Bibliography, page 7

1. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26179907
   Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription.

   Ying Z, Mei M, Zhang P, Liu C, et al. · J Immunol 2015
   used by PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check
2. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26545813
   LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes.

   Singh PK, Plumb MR, et al. · Genes Dev 2015
   used by PSIP1 makes two proteins and only one of them has the IBD: a p52 result is not a p75 result, and the knockout mouse removes both, The third job: LEDGF sits on transcribed gene bodies with splicing factors and changes exon choice in half the genes that have alternative isoforms
3. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25683715
   Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis.

   Antonicka H, Shoubridge EA · Cell Rep 2015
   used by PSIP1-FASTKD2 declined: the bait is a mitochondrial matrix and nucleoid protein with two experimental localisations, the prey is nucleoplasmic LEDGF, and the row is one spoke-expanded BioID2 proximity in K562
4. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25500544
   The landscape and therapeutic relevance of cancer-associated transcript fusions

   Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RGW · Oncogene 2015
   used by Read-through (cis-SAGe) chimeras: most 'fusions' called from RNA-seq in childhood ALL are normal conjoined genes
5. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25629980
   tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia.

   Tao YF, Li ZH, Wang NN, et al., Pan J · Leuk Lymphoma 2015
   used by RPRM (reprimo) - the other half of menin's Ewing 2007 pair, a protein with no experimental localisation at all, and a promoter methylated in 45% of paediatric AML
6. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 26137584
   Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4-MLL Fusion Protein.

   Sabiani S, Geppert T, Engelbrecht C, et al. · EBioMedicine 2015
   used by SIAH1/SIAH2: the disposal route that destroys wild-type AF4 and that the reciprocal fusion escapes, Taspase1 is what turns the reciprocal product into an oncoprotein - and it is a conditional oncogene because of it, The five verdicts in one place, plus what this beat read and did not use
7. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 26671595
   t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.

   L'Abbate A, Tolomeo D, De Astis F, Lonoce A, Lo Cunsolo C, Muhlematter D, Schoumans J, Vandenberghe P, Van Hoof A, Palumbo O, Carella M, Mazza T, Storlazzi CT · Molecular Cancer 2015
   used by SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's
8. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25738358
   C-terminal domain of SMYD3 serves as a unique HSP90-regulated motif in oncogenesis.

   Brown MA, Foreman K, et al. · Oncotarget 2015
   used by SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
9. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25858143
   SOCS2 Controls Proliferation and Stemness of Hematopoietic Cells under Stress Conditions and Its Deregulation Marks Unfavorable Acute Leukemias.

   Vitali C, Bassani C, Chiodoni C, Fellini E, et al. · Cancer Research 2015
   used by SOCS2 (O14508) - a MENIN-INHIBITOR-SELECTIVE member of the signature, a cullin-5 E3 substrate receptor, and its likeliest upstream regulator is MEF2C rather than ATF4
10. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25915022
    The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.

    McHugh CA, Chen CK, Chow A, Surka CF, Tran C, et al. · Nature 2015
    used by SPEN / SHARP / MINT (Q96T58) - the RNA-binding corepressor that silences the X chromosome, in the pan-MLL-fusion core
11. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.journal-articlePMID 25550361
    Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

    Lindsley RC, ..., Ebert BL · Blood 2015
    used by STAG2 - the cohesin subunit that defines secondary AML, and the one whose loss a KMT2A fusion does not care about
12. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 26007649
    Gene target specificity of the Super Elongation Complex (SEC) family: how HIV-1 Tat employs selected SEC members to activate viral transcription

    Lu H, Li Z, Zhang W, Schulze-Gahmen U, Xue Y, Zhou Q · Nucleic Acids Research 43(12):5868-79 2015
    used by Step 3 — The hijack: the fusion drags the super elongation complex to paused RNA polymerase II
13. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25978433
    The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells.

    Lai YS, Chen JY, Tsai HJ, Chen TY, et al. · Blood Cancer Journal 2015
    used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
14. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26214592
    Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

    Fischer U, Forster M, Rinaldi A, Risch T, Sungalee S, Warnatz HJ, Bornhauser B, Gombert M, Kratsch C, Stutz AM, Sultan M, Tchinda J, Worth CL, Amstislavskiy V, et al., Borkhardt A, Bourquin JP, Franke A, Korbel JO, Stanulla M, Yaspo ML · Nat Genet 2015
    used by TCF3::HLF (E2A-HLF), t(17;19)(q22;p13)
15. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 26159857
    Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex.

    Ricketts MD, Frederick B, Hoff H, et al. · Nature Communications 2015
    used by The HUCA complex (HIRA/UBN1/CABIN1/ASF1a) - four proteins, one job: put H3.3 into chromatin without waiting for S phase, UBN1 - the subunit that decides the HIRA complex is carrying H3.3 and not H3.1, by reading a single glycine
16. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 26075887
    Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis.

    Mercer JL, et al. · PLoS One 2015
    used by The non-chromatin half: CALM-AF10 breaks the cell's iron intake and the cells are chelator-sensitive in vitro - but iron restriction did not extend survival in vivo (corrected 2026-09-21)
17. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 26375006
    BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis.

    Canver MC, Smith EC, Sher F, Pinello L, et al. · Nature 2015
    used by The noncoding dependency screen five hypotheses in this graph are waiting on - and the KMT2A-rearranged screen that already exists and bounds it
18. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26593443
    AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

    Okuda H, Kanai A, Ito S, Matsui H, Yokoyama A · Nature Communications 2015
    used by The nucleolus — the one compartment with direct published images of a KMT2A fusion inside it
19. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25343275
    Conditional deletion of Men1 in the pancreatic beta-cell leads to glucagon-expressing tumor development.

    Li F, Su Y, Cheng Y, Jiang X, Peng Y, Li Y, et al. · Endocrinology 2015
    used by The other half of the islet story: losing menin also costs the beta cell its identity and raises glucagon
20. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
    Hein et al. 2015, supplementary workbook mmc4.xlsx, sheet 'HeLa proteome' (copy numbers and concentrations), and mmc2.xlsx, sheet 'bait cell lines'

    · Cell 163(3), supplementary material 2015
    used by The six unwritten DOT1L partners are not six findings - they are nine spokes of ONE GFP-DOT1L pulldown, and the source paper already graded them
21. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 26198043
    Chlorpyrifos Induces MLL Translocations Through Caspase 3-Dependent Genomic Instability and Topoisomerase II Inhibition in Human Fetal Liver Hematopoietic Stem Cells

    Lu C, Liu X, Liu C, et al. · Toxicological sciences : an official journal of the Society of Toxicology 2015
    used by The test bed nobody names: KMT2A rearrangement can be induced and counted in primary human CD34+ and fetal liver stem cells, and it happens without any drug at all
22. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25730767
    Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.

    Izumi K, Nakato R, Zhang Z, Edmondson AC, Noon S, Dulik MC, Rajagopalan R, Venditti CP, Gripp K, Samanich J, Zackai EH, Deardorff MA, Clark D, Allen JL, Dorsett D, Misulovin Z, Komata M, Bando M, Kaur M, Katou Y, Shirahige K, Krantz ID · Nature Genetics 2015
    used by Three of the four AFF scaffolds have a named human Mendelian syndrome and the index fusion's partner has none — a 0/4 that is a fact about AFF1 and not about how hard anyone has looked, What the paralogues' disease biology says about AFF1: the AFF family shares one SIAH degron — and the index fusion DISCARDS it, because the whole degron lies in the AFF1 leader that the junction at residue 347 throws away
23. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 26046368
    Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.

    Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Shimamoto A, Tahara H, Ito E, Kojima S, Kurumizaka H, Ogawa S, Takata M, Yabe H, Yabe M · Am J Hum Genet 2015
    used by UBE2T — E2; rank 33 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
24. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26085575
    AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

    Virts EL, Jankowska A, Mackay C, Glaas MF, Wiek C, Kelich SL, Lottmann N, Kennedy FM, Marchal C, Lehnert E, Scharf RE, Dufour C, Lanciotti M, Farruggia P, Santoro A, Savasan S, Scheckenbach K, Schipper J, Wagenmann M, Lewis T, Leffak M, Farlow JL, Foroud TM, Honisch E, Niederacher D, Chakraborty SC, Vance GH, Pruss D, Timms KM, Lanchbury JS, Alpi AF, Hanenberg H · Hum Mol Genet 2015
    used by UBE2T — E2; rank 33 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
25. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26317469
    The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins.

    Thoms M, Thomson E, Baßler J, Gnädig M, Griesel S, Hurt E · Cell 2015
    used by UTP18 / WDR50 (Q9Y5J1) - the SSU processome subunit that recruits the exosome helicase MTREX to rRNA fragments; in three MLL-fusion interactomes but not the index fusion's, and separately the subject of a 21-year-old IntAct curation error in this graph
26. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25435373
    A small subunit processome protein promotes cancer by altering translation.

    Yang HW, Kim TM, Song SS, Menon L, Jiang X, Huang W, Black PM, Park PJ, Carroll RS, Johnson MD · Oncogene 2015
    used by UTP18 / WDR50 (Q9Y5J1) - the SSU processome subunit that recruits the exosome helicase MTREX to rRNA fragments; in three MLL-fusion interactomes but not the index fusion's, and separately the subject of a 21-year-old IntAct curation error in this graph
27. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 26167872
    Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

    Grebien F, Vedadi M, et al. · Nature chemical biology 2015
    used by WDR5 maintains a differentiation block — in CEBPA p30 AML, not in KMT2A-rearranged disease, and a title check nearly buried it
28. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 26329759
    AF4 and AF4-MLL mediate transcriptional elongation of 5-lipoxygenase mRNA by 1, 25-dihydroxyvitamin D3.

    Ahmad K, Scholz B, Capelo R, et al. · Oncotarget 2015
    used by What the reciprocal product assembles: P-TEFb, an H3K4 methyltransferase, an H3K79 methyltransferase, an arginine methyltransferase and an acetyltransferase
29. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24695851
    MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia

    Manara E, et al. · Blood 2014
    used by 'AF4 bodies' - a named subnuclear compartment that is non-nucleolar and coincident with no known nuclear structure, and the one place a KMT2A fusion has been shown to move a partner, A partner's 'normal' compartment is usually read off a different tissue, and for at least two KMT2A partners that reading is wrong in blood cells, A three-question triage to detect subtraction mechanisms, applied to every KMT2A partner in the graph, AFDN (AF6): nothing is discarded from the fusion, yet this is the clearest subtraction in the set — the fusion steals wild-type AF6 out of the cytoplasm, Cytoplasmic localisation in KMT2A fusions: the SEPTIN case has an image, the GPHN case has none, and neither partner wins the compartment, How a cytoskeletal partner reaches chromatin at all — the KMT2A N-terminus drags it in, and the traffic runs both ways, How general is subtraction across KMT2A fusions? Common enough to matter, too heterogeneous to be one thing, and mostly invisible to the way this project searches, KMT2A::AFDN (MLL-AF6), t(6;11)(q27;q23), Subtraction is a partner class, not a curiosity — and the class is defined by compartment, not by sequence
30. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24397609
    Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.

    Suzuki M, et al. · Cancer Sci 2014
    used by A ten-residue export signal is the 5' partner's whole contribution - and the field disagrees about which direction it pushes, CALM-AF10 is predominantly cytoplasmic in transfected non-haematopoietic cells - and NUCLEAR in leukaemia cells (title corrected 2026-09-21; the five systems are five instances of one design)
31. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24727379
    Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4.

    Gu J, et al. · Cell Cycle 2014
    used by AFF1- and AFF4-containing super elongation complexes occupy physically distinct neighbourhoods in living cells, and KMT2A::AFF1 inherits the AFF1 one
32. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24764564
    Requirement for CDK6 in MLL-rearranged acute myeloid leukemia

    Placke T, Faber K, Nonami A, Putwain SL, Salih HR, Heidel FH, Kramer A, Root DE, Barbie DA, Krivtsov AV, Armstrong SA, Hahn WC, Huntly BJ, Sykes SM, Milsom MD, Scholl C, Frohling S · Blood 124:13-23 2014
    used by AMLSG 23-14 / Palbo-AL-1 (NCT02310243) — the only trial ever run in MLL-rearranged acute leukemia with a CDK4/6 inhibitor, and it reported nothing, CCND3 (cyclin D3) — the scan's rank-4 hit, and the only one of the four with a drug class already in children, CDK4 - the other half of the class name, and it is NOT the gene this disease needs, CDK4/6 inhibition in KMT2A-rearranged leukemia — the class was already tried, and the trial never reported, CDK6 - the kinase the KMT2A-r rationale actually rests on, and the pan-essentiality flag and the selectivity are both true, The G1 state in KMT2A-rearranged leukaemia — where CDK6 does a job that is not about the cell cycle at all
33. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24310817
    Clustering of genomic breakpoints at the MLL locus in therapy-related acute leukemia with t(4;11)(q21;q23)

    Hasan SK, Barba G, Metzler M, et al. · Genes, chromosomes & cancer 2014
    used by Analysis (runnable): mine the KMT2A junction sequences for repair-pathway signature, and count the one junction class with a genetic control behind it
34. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25201414
    Chromosomal translocations in human cells are generated by canonical nonhomologous end-joining

    Ghezraoui H, Piganeau M, Renouf B, et al. · Molecular cell 2014
    used by Analysis (runnable): mine the KMT2A junction sequences for repair-pathway signature, and count the one junction class with a genetic control behind it, Which repair pathway glues the fusion together: classical NHEJ vs alternative end joining
35. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25245097
    Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells

    Zeng C, Xu Y, Xu L, Yu X, Cheng J, Yang L, Chen S, Li Y · BMC Cancer 2014
    used by Analysis: does the fusion's target set sit at lamina-associated domain borders? A free overlay of published LAD maps on published fusion occupancy, Hypothesis: KMT2A::AFF1 mislocalises to or disrupts nuclear speckles, and paraspeckle biology (NEAT1) is a fusion-repressed differentiation brake, Paraspeckles and NEAT1 — no KMT2A evidence at all, but a fusion oncoprotein in another leukemia uses NEAT1 as a differentiation brake
36. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24463511
    ANP32E is a histone chaperone that removes H2A.Z from chromatin.

    Obri A, Ouararhni K, Papin C, et al. · Nature 2014
    used by ANP32E - the eviction chaperone: the only protein in this beat whose job is to take a histone variant OUT of chromatin, H2AZ1 - the one histone variant with a direct KMT2A-fusion paper: MLL-AF10 and MLL-ENL recruit Tip60 to Hoxa9 to acetylate H2A.Z
37. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24680668
    A non-active-site SET domain surface crucial for the interaction of MLL1 and the RbBP5/Ash2L heterodimer within MLL family core complexes.

    Shinsky SA, Hu M, Vought VE, Ng SB, Bamshad MJ, Shendure J, Cosgrove MS · Journal of Molecular Biology 2014
    used by ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, ASH2L: the only WRAD subunit ever perturbed in a KMT2A::AFF1 cell, once, weakly, DPY30 aims the H3K4 machinery while ASH2L powers it, which is why only DPY30 tracks menin, RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum
38. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24389101
    Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia

    Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S, Liu L, Chen Y, et al. (Dou Y, senior author) · Molecular Cell 53:247-61 2014
    used by ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, DPY30 — the smallest COMPASS subunit, and the only one that behaves like a selective dependency, Lost from the KMT2A half: the SET domain (aa 3829-3945) - the lost module whose loss demonstrably does not matter, Lost from the KMT2A half: the WIN motif and the whole WRAD interface (aa 3762-3767, Arg3765), RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, The third category: modules lost from the fusion protein but supplied in trans by the wild-type KMT2A allele, WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away
39. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25083873
    ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress.

    Kumar A, Mazzanti M, Mistrik M, Kosar M, Beznoussenko GV, Mironov AA, Garrè M, Parazzoli D, Shivashankar GV, Scita G, Bartek J, Foiani M · Cell 2014
    used by ATR - the replication-stress kinase with the best preclinical case in this disease and the best published reason not to inhibit it
40. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25099282
    Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour

    Hanks S, Perdeaux ER, Seal S, et al. · Nature Communications 2014
    used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails
41. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25238757
    Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response

    Park KS, Bayles I, Szlachta-McGinn A, et al. · Journal of Immunology 2014
    used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails, ELL2 — a SEC subunit that almost no cell needs, next to a paralogue almost every cell needs, Target safety triage v2: constraint with its uncertainty attached (run), The bite-back of striking a target: a wrong strike costs a cure and generates no data that it was wrong
42. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24813891
    The histone methyltransferase activity of MLL1 is dispensable for hematopoiesis and leukemogenesis

    Mishra BP, Zaffuto KM, Artinger EL, et al. · Cell Reports 2014
    used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails, BOD1L (BOD1L1) — the top SETD1A co-dependency, and the only candidate in this cycle tested by CRISPR tiling in a KMT2A::AFF1 line, Does the fusion 'lose restraint'? The pattern of KMT2A-side loss, and why the tidy reading does not survive contact with the ledger, H3K4me2 - the LSD1 substrate, and the only histone mark ever compared head-to-head between two KMT2A fusion partners in human cells, H4K16ac - the one mark rule 80 actually rescued in this beat: elevated at MLL-AF9 targets in a supplementary figure, and the reason MLL1's own enzyme turns out to be dispensable, Import class 1: murine MLL-AF9 myeloid transformation, the field's default assay and this graph's largest single import, KMT2A / MLL1 — the gene that breaks, KMT2A is called an H3K4 methyltransferase, and it is required for the mark at under 5% of the promoters that carry it, Lost from the KMT2A half: the MOF/KAT8 contact - required in the cell, but not shown to matter to the fusion, Lost from the KMT2A half: the SET domain (aa 3829-3945) - the lost module whose loss demonstrably does not matter, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum, The lost SET domain, and the verdict: the fusion is a gain-of-function neomorph, not a KMT2A loss-of-function, The phase-2 go/no-go register: the numbers we agree to before we look, Verdict on the WRAD contradiction: the graph is right, its citation class is wrong, and its universal is wrong
43. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24498346
    Homeodomain transcription factor Meis1 is a critical regulator of adult bone marrow hematopoiesis

    See PubMed record PMID 24498346 for the full author list (not transcribed here) · PLoS One 2014
    used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails
44. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24441288
    Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031

    Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Zheng HW, Davies SM, Gaynon PS, Trigg M, Rutledge R, Jorstad D, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B · Leukemia 2014
    used by BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11), Imatinib: one molecule, three unrelated rare diseases, twenty years of cross-subsidy
45. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25464900
    AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.

    Deshpande AJ, et al. · Cancer Cell 2014
    used by Bite-back: a DOT1L inhibitor in CALM-AF10 deepens a genome-wide H3K79 deficit that already causes chromosome breaks, Bivalent and primed chromatin at fusion target loci — and why the H3K4/H3K27 story is weaker than usually told, H3K79me1 - the first methyl group, the one H2B ubiquitination is not needed for, and the state HOX loci fall back to as blood cells mature, How much of this graph's mechanism is somebody else's fusion? A counted answer: 54% of fusion-bearing evidence, and 0% from a dedicated human KMT2A::AFF1 experiment, Import class 3: the DOT1L-AF10 coiled-coil axis, an MLLT10 mechanism with no counterpart in the index fusion, KMT2A::MLLT10 (MLL-AF10), t(10;11)(p12;q23), Losing the AF10 PZP reader is not a missing function - it is a removed brake, and putting it back cures the fusion, Menin inhibitors should leave half the H3K79 methylation standing - and if they do not, the menin-interface model is wrong somewhere, Partner import: when a mechanism measured in one fusion is asserted about another, Repeat the H3K79 partition in a human KMT2A::AFF1 line: menin inhibition and MLLT10 knockout, side by side with a KMT2A::MLLT3 line, Step 5 — The output program: HOXA9/HOXA10/MEIS1/PBX3 plus MEF2C, MYB, BCL2, FLT3 and PROM1/CD133, The DOT1L-AF10 octamer - the second route to H3K79 methylation, required in MLL-AF10 and absent from KMT2A::AFF1
46. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24798348
    A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma.

    Habineza Ndikuyeze G, Gaurnier-Hausser A, ... Mason NJ · PLoS One 2014
    used by Blocking IKK/NF-kB in an infant is removing the switch every immune cell runs on — and the class has already failed clinically on exactly that, IKBKG (NEMO) — the scaffold that makes the canonical complex a complex, and a symbol that returns ZERO records in this disease
47. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24590072
    Direct measurement of local oxygen concentration in the bone marrow of live animals

    Spencer JA, Ferraro F, Roussakis E, Klein A, Wu J, Runnels JM, et al. · Nature 2014
    used by Bone-marrow sinusoidal endothelial cell — the vessel wall that keeps stem cells alive, and posts vesicles that accelerate MLL-AF9 leukaemia, NG2+ periarteriolar pericyte — the cell that holds blood stem cells asleep, and the one MLL-AF9 leukaemia destroys, The bone-marrow niche — the address a blood stem cell lives at, which 26 entries in this graph invoke and none had defined, The endosteal niche — the bone surface, where leukaemia-initiating cells were imaged homing and dividing symmetrically, The marrow oxygen gradient — low everywhere, lowest at the sinusoids, and in this leukaemia low oxygen helps the drug rather than the cell, The perivascular and sinusoidal niche — where the functional evidence actually sits, and where the marrow is genuinely hypoxic
48. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24735925
    Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4.

    Liu H, Westergard TD, ... Hsieh JJ · Cancer Cell 2014
    used by Bortezomib is called an NF-kB inhibitor, and in MLL leukaemia it does two different things in two lineages — neither of which is reliably NF-kB in the lymphoid one, PAX5 - the most frequently hit non-KMT2A gene in infant KMT2A-rearranged ALL, and it is a deletion in one allele, not a mutation
49. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24140279
    Methylation of the DNA/RNA-binding protein Kin17 by METTL22 affects its association with chromatin.

    Cloutier P, Lavallee-Adam M, Faubert D, et al. (5 authors; senior author Coulombe B) · J Proteomics 2014
    used by BUD13 - a RES-complex splicing factor 1.66 Mb from KMT2A on 11q23.3, whose one chromatin paper puts it in the soluble fraction
50. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24997988
    The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.

    Thauvin-Robinet C, Lee JS, Lopez E et al · Nature Genetics 2014
    used by C2CD3 - the centriole-elongation regulator fused to KMT2A exon 8 in an MPNST, predicted OUT OF FRAME, and the partner whose RefSeq transcript is 390 residues shorter than UniProt's canonical
51. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24460908
    PRC1 components exhibit different binding kinetics in Polycomb bodies.

    Vandenbunder B, Fourré N, Leray A, Mueller F, Völkel P, Angrand PO, Héliot L · Biol Cell 2014
    used by CBX8 — the one place in this interactome where two good papers flatly disagree, and DepMap takes a side, RING1 (RING1A) - the paralogue that is not RING1B, and the reason a substring search for 'RING1' in this graph returns the wrong gene
52. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24736461
    MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL

    van der Linden MH, Willekes M, van Roon E, Seslija L, Schneider P, Pieters R, Stam RW · Cell Cycle 13:834-844 2014
    used by CCND3 (cyclin D3) — the scan's rank-4 hit, and the only one of the four with a drug class already in children, CDK4 - the other half of the class name, and it is NOT the gene this disease needs, CDK4/6 inhibition in KMT2A-rearranged leukemia — the class was already tried, and the trial never reported, CDK6 - the kinase the KMT2A-r rationale actually rests on, and the pan-essentiality flag and the selectivity are both true, The G1 state in KMT2A-rearranged leukaemia — where CDK6 does a job that is not about the cell cycle at all
53. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24367103
    AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation.

    Lu H, Li Z, Xue Y, Schulze-Gahmen U, Johnson JR, Krogan NJ, Alber T, Zhou Q · Proc Natl Acad Sci U S A 2014
    used by CCNT2 / cyclin T2 - expressed in every KMT2A-rearranged line and needed by none of them, so the cyclin T split is real rather than an expression artefact, CDK9 - the kinase the whole SEC story runs through, which this graph held only as half of a two-protein summary entry, DDX6 - the only protein ever proposed to do for a cell what Tat does for the virus, on the strength of one 2016 paper, Directed extraction of P-TEFb from the reservoir: HIV-1 Tat is the worked example, and the only cellular candidate rests on one unreplicated paper, How P-TEFb gets out of the reservoir: a dephosphorylation, a dissociation, and a reassembly on whichever scaffold is waiting, The 7SK snRNP - a stable RNA core with a reversibly docked kinase, which is why the reservoir is a switch and not a sink, The fusion begins at AFF1 residue 347 and the cyclin T1-binding sequence ends at 308, so KMT2A::AFF1 is the one AFF-family protein that cannot enter the reservoir, The two t(4;11) products split AFF1 exactly at the P-TEFb-binding module, and the elongation half goes to the reciprocal
54. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24662513
    The structure and substrate specificity of human Cdk12/Cyclin K.

    Bosken CA, Farnung L, Hintermair C, Merzel Schachter M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick D, Geyer M · Nat Commun 2014
    used by CDK12 - a different kinase with a different cyclin, and in KMT2A-rearranged lines it is an anti-dependency
55. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24612037
    Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16.

    · Cancer Sci 2014
    used by CDKN2A - one gene, two reviewed UniProt records with the same primary symbol, and a deletion that is three times rarer here than in the infant leukaemias next door
56. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25017722
    Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche

    Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, et al., Frenette PS · Cell Stem Cell 2014
    used by Cell identities considered and not written: what the search actually returned for basophils, mast cells, eosinophils, NK cells and the rest, Experiment: block the beta-2 adrenergic receptor in a KMT2A-rearranged model — the leukaemogenic nerve signal runs through a receptor an old, cheap, infant-licensed drug already hits, Hypothesis: treatment-remodelled niche, not niche-imposed dormancy, is what residual KMT2A-rearranged disease exploits, MLL-AF9 leukaemia destroys the nerves that run its own niche — a mechanism class this graph had nothing on, Nestin+ mesenchymal stem cell — the niche cell that MLL-AF9 leukaemia wakes up and then loses, NG2+ periarteriolar pericyte — the cell that holds blood stem cells asleep, and the one MLL-AF9 leukaemia destroys, Sympathetic nerve fibre in bone marrow — the wiring that sets the niche's daily rhythm, through beta-3 in health and beta-2 in leukaemia
57. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24335498
    Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications

    Thol F, Bollin R, Gehlhaar M, Walter C, Dugas M, Suchanek KJ, Kirchner A, Huang L, Chaturvedi A, Wichmann M, Wiehlmann L, Shahswar R, Damm F, Göhring G, Schlegelberger B, Schlenk R, Döhner K, Döhner H, Krauter J, Ganser A, Heuser M · Blood 2014
    used by Cohesin as an architectural co-lesion class — mutated in AML, associated with NPM1 rather than KMT2A, and leukemogenic on partial loss
58. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 25033907
    Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny.

    Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, et al., Yona S · Nat Rev Immunol 2014
    used by Conventional (myeloid-related) dendritic cell - the DC lineage RELB actually builds, and the thymic part of that phenotype is architecture rather than a cell-intrinsic requirement
59. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 25085016
    CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients.

    Li S, Fan R, et al. · Leuk Res 2014
    used by CXXC4 (IDAX) - TET2's CXXC domain, sitting on a separate gene after an evolutionary inversion, and annotated cytoplasmic only by similarity
60. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25049225
    The PML-associated protein DEK regulates the balance of H3.3 loading on chromatin and is important for telomere integrity.

    Ivanauskiene K, Delbarre E, McGhie JD, Kuntziger T, Wong LH, Collas P · Genome Research 2014
    used by DEK - a chromatin architectural protein that gatekeeps H3.3 and boosts HP1alpha, is a fusion partner in its own right, and is the substrate behind this graph's third CK2 route
61. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24465000
    MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters.

    Okuda H, Kawaguchi M, et al. · Nucleic Acids Res 2014
    used by Does the fusion need the PWWP arm? An artificial CXXC + H3K36me2-reader + AF4-interaction protein substitutes for a whole MLL fusion - but LEDGF itself is not required for the fusion to reach chromatin, You can lower LEDGF without a LEDGF ligand: its protein half-life is about 4 hours against a proteome average of 20, so blocking guanine nucleotide or rRNA synthesis takes it out first
62. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24788516
    Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex

    Dias J, Van Nguyen N, Georgiev P, Gaub A, Brettschneider J, Cusack S, Kadlec J, Akhtar A · Genes & Development 28(9):929-42 2014
    used by Does WDR5 move between complexes? An acute KANSL1 degron with WDR5 co-IP, WDR5 CUT&RUN and H4K5/K8/K16ac readout in a KMT2A-rearranged line, KANSL1 - the NSL scaffold, and the protein through which WDR5 binding to NSL and to MLL/COMPASS is mutually exclusive, KANSL2 - the second NSL subunit in the WDR5 structure, with one leukaemia record and a dependency profile that is the mirror image of a selective target, NSL complex - the MOF assembly that five NUP98 fusions bind alongside MLL1, and that competes with MLL/COMPASS for WDR5, WDR5 is partitioned, not shared: NSL and SET1/MLL complexes compete for one pool, so perturbing NSL changes how much WDR5 reaches the wild-type KMT2A complex the fusion depends on
63. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25139354
    The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells.

    Yang Z, Augustin J, Chang C, Hu J, Shah K, Chang CW, Townes T, Jiang H · Blood 2014
    used by DPY30 — the smallest COMPASS subunit, and the only one that behaves like a selective dependency, DPY30: the founding negative does not cover it, and it has no KMT2A contact to lose, Separate positioning from catalysis: an ASH2L mutant that keeps RBBP5 and loses DPY30
64. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25456412
    Molecular basis for DPY-30 association to COMPASS-like and NURF complexes.

    Tremblay V, Zhang P, Chaturvedi CP, et al. · Structure 2014
    used by DPY30 D/D domain and the ASH2L SDI helix: four hydrophobic pockets, one load-bearing leucine - and a 94-residue numbering offset that relocates the whole motif
65. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PDB 4RIQ: Crystal structure of DPY-30 dimerization/docking domain in complex with Ash2L Sdc1-DPY-30 Interacting region (SDI)

    Tremblay V, Zhang P, Chaturvedi CP, et al. · RCSB Protein Data Bank 2014
    used by DPY30 D/D domain and the ASH2L SDI helix: four hydrophobic pockets, one load-bearing leucine - and a 94-residue numbering offset that relocates the whole motif
66. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25305204
    The same site on the integrase-binding domain of lens epithelium-derived growth factor is a therapeutic target for MLL leukemia and HIV.

    Murai MJ, Pollock J, et al. · Blood 2014
    used by Ebselen: the only small molecule reported to bind LEDGF itself - and it does it by making selenium-sulphur bonds with whatever thiols it meets, HDGFL2 / HRP-2 - the second IBD protein, which binds KMT2A at the same site with the same affinity and does NOT need menin to do it, HIV-1 integrase on the LEDGF IBD: the same pocket as KMT2A, a thousandfold tighter, and a published competition that displaces the leukaemic complex at IC50 301 nM, Hypothesis: LEDGF licenses elongation at fusion target genes rather than anchoring the fusion, which predicts that a LEDGF agent is epistatic with BET and CDK9 inhibition and invisible in a fusion-ChIP assay, LEDGF IBD to KMT2A: TWO motifs, not one - IBM1 at 124-133 and IBM2 at 147-152, and the Kd this graph recorded as missing is 14.7 uM, LEDGF occupancy under revumenib: the measurement the graph called missing exists, in one 2025 preprint, and it goes the way the tenfold cooperativity predicts, Menin and LEDGF hold WILD-TYPE KMT2A on chromatin; for the fusion LEDGF is functionally required but positionally dispensable, The clearest clinical rationale for a LEDGF agent - second line after menin-inhibitor failure - has never been tested, and one 2025 measurement now argues against it, The HIV field is NOT drugging LEDGF: LEDGINs and ALLINIs bind integrase, and the proof is that they still work in a LEDGF knockout cell, The LEDGF hole, measured: every published LEDGF-removal experiment removes it BEFORE or AT transformation, and none treats an established leukaemia in an animal, The LEDGF IBD–KMT2A grip: the second half of the clamp, and nobody is drugging it, Three routes to one observation: the CUT&RUN panel that says whether menin eviction, H3K36me3 loss or MLL loss takes LEDGF off the fusion's genes, What was searched for a structure and what came back empty: the KMT2A interface layer enumerated by accession pair, with the graph's own unmapped interfaces listed
67. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24532712
    The methyltransferase G9a regulates HoxA9-dependent transcription in AML.

    Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L, Zhang R, Krosl J, Yung E, Kirschner J, Rosten P, Underhill TM, Jin J, Hebert J, Sauvageau G, Humphries RK, Rossi FM · Genes and Development 2014
    used by EHMT2 / G9a - the H3K9me1/2 writer that sets whether the KMT2A LOCUS ITSELF rearranges, and whose loss delays MLL-AF9 AML in a supplementary figure nobody can find
68. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25437568
    Quantitative ChIP-Seq normalization reveals global modulation of the epigenome

    Orlando DA, Chen MW, Brown VE, et al. · Cell Reports 2014
    used by Eighteen libraries, no replicate: what the only absolute-scale chromatin dataset in this project is structurally unable to say, and why this project's own floors may not be borrowed to fill the gap, Every per-sample normalisation is a constant multiplier: it never changes the shape, it only moves the line between 'gained' and 'lost' - which is why 'share', 'raw' and 'absolute' give the same ranking and three different answers to 'did this go up?', The missing reagent is a spike-in, not a better statistic: a spike-in-normalised H3K4me3, H3K79me2 and H3K27me3 ChIP-seq at 72 h of a clinical menin inhibitor in a KMT2A-rearranged human line, which is the only design that can tell a genuine genome-wide mark redistribution from the compositional shadow of a peak-localised change
69. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24166297
    Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells.

    Huang X, Spencer GJ, Lynch JT, et al. · Leukemia 2014
    used by EP400 - the ATPase that swaps H2A.Z in; its complex is required by MLL leukaemia stem cells, and in DepMap it is one of the three genes LEAST required in KMT2A-rearranged lines
70. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24451543
    Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.

    · Nature 2014
    used by ESR1 / estrogen receptor alpha - menin's best-documented non-leukaemic partner, and the only one a menin inhibitor is being given to patients to disrupt on purpose
71. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24240202
    Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells

    Montes R, Ayllon V, Prieto C, Bursen A, Prelle C, Romero-Moya D, et al. · Leukemia 2014
    used by Experiment: does MLL-AF4 transform a staged fetal progenitor when it cannot transform cord blood?, Hypothesis: the second hit in infant KMT2A-rearranged leukaemia is a fetal developmental window, not a mutation, What fraction of fusion-positive newborns ever get leukaemia? For ETV6::RUNX1, very few. For KMT2A, nobody knows, and the biology says the answer may be most of them, When one thing goes wrong, do several? In infant KMT2A-rearranged leukaemia the answer is no, and that cuts against the intuition
72. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25267198
    FOXP1 directly represses transcription of proapoptotic genes and cooperates with NF-kB to promote survival of human B cells

    van Keimpema M, Grüneberg LJ, Mokry M, van Boxtel R, Koster J, Coffer PJ, et al. · Blood 2014
    used by FOXP1 - the forkhead repressor that licenses the pro-B to pre-B transition and blocks apoptosis with NF-kB, sitting at a 105x MLL1-N bin in a leukaemia whose defining lesion is a pro-B arrest
73. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24703711
    A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

    Gröschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BAM, Erpelinck C, van der Velden VHJ, Havermans M, et al. · Cell 157:369-381 2014
    used by GATA2 - the least KMT2A-selective gene on this beat, ranking 17,591 of 17,728, and a factor whose leukaemia biology is about stemness and chemoresistance rather than about the fusion, Mechanism class 5 — enhancer hijacking (inv(3) GATA2/EVI1 — and DUX4-r, which only half belongs here)
74. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24211311
    A comparative study of nucleostemin family members in zebrafish reveals specific roles in ribosome biogenesis.

    Essers PB, Pereboom TC, Goos YJ, Paridaen JT, Macinnes AW · Dev Biol 2014
    used by GNL2 / Ngp-1 (Q13823) - a nucleostemin-family nucleolar GTPase in the MLL-fusion nucleolar block, in the index fusion's column at p = 0.0492, and the one member with a published granular-component assignment
75. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24613878
    Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z.

    Mao Z; Pan L; Wang W; Sun J; Shan S; Dong Q; et al. · Cell Res 2014
    used by H2A.Z - two genes of identical length, one KMT2A paper, and the measured quantity is a ratio nobody has repeated
76. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24837678
    H2B ubiquitylation promotes RNA Pol II processivity via PAF1 and pTEFb.

    Wu L, Li L, Zhou B, Qin Z, Dou Y · Mol Cell 2014
    used by H2BK120ub (H2Bub1) — the ubiquitin tag on histone H2B that licenses H3K79 methylation, and the mark this graph was missing, H2BK34ub — a second ubiquitination site on H2B that also stimulates DOT1L, written by MSL1/MSL2, and important at HOXA9 and MEIS1
77. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24710217
    The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes.

    Huether R; Dong L; Chen X; Wu G; Parker M; Wei L; et al. · Nat Commun 2014
    used by H3.3 - the graph's most-named epigenetic object with no entry, 325 mentions, and not one measurement in a KMT2A-rearranged cell
78. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25417107
    AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation.

    Li Y; Wen H; Xi Y; Tanaka K; Wang H; Peng D; et al. · Cell 2014
    used by H3K27ac - named in 40 entries with no entry of its own, and the strongest KMT2A::AFF1 measurement of it is invisible to every abstract search, H3K9ac - the mark KMT2A fusions pile up on their own targets, the one the AF9 reader actually binds, and the one a DOT1L inhibitor strips off first, KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3), MLLT3 (AF9): the YEATS acetyl-lysine reader is discarded in ~92% of MLL-AF9 patients — same shape as PZP, but the causal test has never been run, MLLT3 / AF9 — a famous fusion partner that is not a dependency, and a hub domain that is, Restore the AF9 YEATS reader in cis to MLL-AF9, and read out the ENL patients who already did the experiment for us
79. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24769646
    Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region.

    Sakamoto K; Imamura T; Yano M; Yoshida H; Fujiki A; Hirashima Y; et al. · Blood Cancer J 2014
    used by H3K4me2 - the LSD1 substrate, and the only histone mark ever compared head-to-head between two KMT2A fusion partners in human cells
80. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25402609
    Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wild-type MLL.

    Ahmad K, Katryniok C, Scholz B, Merkens J, Loscher D, Marschalek R, et al. · Oncogenesis 3(11):e127 2014
    used by HDAC1 - a class I eraser that has no dependency claim of its own in this disease, because removing it alone does nothing until HDAC2 goes too, HDAC3 - the only HDAC in this disease whose requirement was established genetically rather than by a drug, and the same experiment shows it is not fusion-specific, What the reciprocal product assembles: P-TEFb, an H3K4 methyltransferase, an H3K79 methyltransferase, an arginine methyltransferase and an acetyltransferase
81. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24515107
    Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription.

    Liu P, Xiang Y, Fujinaga K, Bartholomeeusen K, Nilson KA, Price DH, Peterlin BM · J Biol Chem 2014
    used by HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less, HEXIM2 - the paralogue that holds the bound P-TEFb pool constant when HEXIM1 is removed, which is why single-gene experiments on this axis read flat, How P-TEFb gets out of the reservoir: a dephosphorylation, a dissociation, and a reassembly on whichever scaffold is waiting
82. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24503105
    Lead optimization of HMBA to develop potent HEXIM1 inducers.

    Zhong B, Lama R, Ketchart W, Montano MM, Su B · Bioorg Med Chem Lett 2014
    used by HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less, Raising HEXIM1 to brake the fusion's output without touching the fusion - one supporting experiment, one chemical series, and no therapeutic window
83. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 24691255
    The biogenesis of chromosome translocations

    Roukos V, Misteli T · Nature Cell Biology 2014
    used by How a chromosome translocation actually forms: proximity + breakage + repair, Why KMT2A picks AFF1: spatial proximity, shared transcription hubs, and the unsettled proximity-versus-damage question
84. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24478402
    Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance.

    Buscarlet M, Krasteva V, Ho L, Simon C, et al. · Blood 2014
    used by How BAF maintains KMT2A-rearranged leukaemia: it holds the blast undifferentiated, and it does so in other leukaemias too, SMARCA2 (BRM) - the paralogue nobody measured, and the reason a DepMap rank cannot predict what a BRG1/BRM inhibitor does
85. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25517963
    Targeting beta-catenin signalling for therapeutic intervention in MEN1-deficient pancreatic neuroendocrine tumours

    Jiang X, Cao Y, Li F, Su Y, Li Y, Peng Y, Cheng Y, Zhang C, Wang W, Ning G · Nat Commun 5:5809 2014
    used by How long does menin have to be gone? Two months in a mouse islet, a decade or more in a human carrier, Turn menin off for a defined window, then back on: the missing experiment that would bound reversibility
86. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25275444
    Mechanism of suppression of chromosomal instability by DNA polymerase POLQ

    Yousefzadeh MJ, Wyatt DW, Takata K, et al. · PLoS genetics 2014
    used by Hypothesis: the KMT2A break can be prevented rather than the fusion treated - stated so it can be killed, and it probably should be
87. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24316986
    Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.

    Ko CI, Wang Q, Fan Y, Xia Y, Puga A · Stem Cell Res 2014
    used by In inv(16), disrupting the fusion interface swaps BRG1 for RING1B at three MYC enhancers - the cleanest version anywhere of the experiment nobody has run on menin, Q50 enumeration: every query this beat ran, every zero it recorded with its bound, and the papers it read and did not use
88. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25016062
    Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors.

    Wächter K, Kowarz E, Marschalek R · Cancer Lett 2014
    used by In the only panel that tested both halves of four translocations, 3 of 4 reciprocal fusions transformed and only 1 of 4 direct ones did, KMT2A*: a menin-blind, LEDGF-blind, SET-competent KMT2A protein made from out-of-frame reciprocal alleles
89. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24336127
    In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity.

    Nakata J, Nakano K, Okumura A, Mizutani Y, Kinoshita H, Iwai M, et al. · Leukemia 2014
    used by In this fusion family, MHC class I is not silenced - it is elevated and load-bearing, holding NK cells off the leukaemia stem cell, The NK cell - the effector arm of haploidentical transplant, the one this disease is documented to evade, and the cell CLEC12A was named on
90. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24413735
    RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia

    Papaemmanuil E, Rapado I, Li Y, Greaves M, Campbell PJ, et al. · Nature Genetics 2014
    used by Is fusion intended in biology sometimes? Yes, and the answer has a strategic edge, Programmed DNA breaks - V(D)J and class switching - and the verdict on whether either one breaks KMT2A, RAG off-target activity: the dominant mutator in ETV6::RUNX1 ALL, and probably not the cause of KMT2A fusions, V(D)J recombination: the immune system deliberately cuts its own chromosomes, using a domesticated transposon
91. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24501218
    shRNA screening identifies JMJD1C as being required for leukemia maintenance.

    Sroczynska P; Cruickshank VA; Bukowski JP; Miyagi S; Bagger FO; Walfridsson J; et al. · Blood 2014
    used by JDI-12 - published as a JMJD1C inhibitor that preferentially kills KMT2A-rearranged leukaemia and spares cord blood, then used as 'KDM3i' to CREATE KMT2A rearrangements in cord-blood progenitors, by two papers that do not cite each other, JMJD1C / KDM3C - named in three entries of this graph as one of the only loci that loses fusion occupancy under a menin inhibitor, ranked 23rd of 17,728 for KMT2A-selective dependency in this project's own scan, with the strongest published shRNA effect in SEM - and no entry until now, One demethylase family sits at both ends of this disease - KDM3B gates whether KMT2A rearranges, JMJD1C is what the resulting fusion needs to survive - and a single compound hits both, so its therapeutic index runs in opposite directions in the two cell populations it reaches
92. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24662245
    Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.

    Mar BG, Bullinger LB, McLean KM, Grauman PV, Harris MH, Stevenson K, et al., Ebert BL, Armstrong SA · Nature Communications 2014
    used by KDM6A / UTX — a commonly asserted KMT2A partner that belongs to a different complex and points the opposite way
93. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25031740
    Homozygous inv(11)(q21q23) and MLL gene rearrangement in two patients with myeloid neoplasms.

    Tang G, Lu X, Wang SA, Roney EK, Zhang L, Hu S, Lu G, Medeiros LJ, Patel A · International Journal of Clinical and Experimental Pathology 2014
    used by KMT2A::MAML2, inv(11)(q21q23) - a therapy-related fusion that also causes a solid tumour
94. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23725386
    MLL-SEPT5 fusion transcript in infant acute myeloid leukemia with t(11;22)(q23;q11).

    Launay E, Henry C, Meyer C, et al. · Leuk Lymphoma 2014
    used by KMT2A::SEPTIN5 (MLL-SEPT5 / MLL-hCDCrel-1), t(11;22)(q23;q11.2)
95. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24794707
    MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia.

    Chen C, Liu Y, Rappaport AR, et al. · Cancer Cell 2014
    used by KMT2C (MLL3) - the fetal brake on MLL-rearranged leukaemia, and a 7q tumour suppressor chemotherapy selects against
96. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24301523
    Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children's Oncology Group report.

    Valentine MC, Linabery AM, Chasnoff S, et al. · Leukemia 2014
    used by KMT2C (MLL3) - the fetal brake on MLL-rearranged leukaemia, and a 7q tumour suppressor chemotherapy selects against
97. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25082813
    Validation and structural characterization of the LEDGF/p75-MLL interface as a new target for the treatment of MLL-dependent leukemia.

    Cermakova K, Tesina P, Demeulemeester J, et al. · Cancer Res 2014
    used by LEDGF IBD to KMT2A: TWO motifs, not one - IBM1 at 124-133 and IBM2 at 147-152, and the Kd this graph recorded as missing is 14.7 uM, Model: interface hotspot prediction - trainable in general, pure extrapolation here, because SKEMPI contains zero menin entries, Phase-2 dossier: the LEDGF/PSIP1 IBD - the best therapeutic index in the interactome, a solved structure, two hotspot residues, and three compounds in the world, PSIP1 / LEDGF p75 — the tether with the best therapeutic index in the whole interactome, Sequencing phase 2: the order to do things in, ranked by information per unit cost, The LEDGF hole, measured: every published LEDGF-removal experiment removes it BEFORE or AT transformation, and none treats an established leukaemia in an animal, The LEDGF IBD–KMT2A grip: the second half of the clamp, and nobody is drugging it
98. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PDB 2MTN: Solution structure of MLL-IBD complex

    Murai MJ, Pollock J, He S, et al. · RCSB Protein Data Bank 2014
    used by LEDGF IBD to KMT2A: TWO motifs, not one - IBM1 at 124-133 and IBM2 at 147-152, and the Kd this graph recorded as missing is 14.7 uM
99. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24270738
    miR-9 is a tumor suppressor in pediatric AML with t(8;21).

    Emmrich S, Katsman-Kuipers JE, Henke K, Khatib ME, Jammal R, Engeland F, Dasci F, Zwaan CM, den Boer ML, Verboon L, Stary J, Baruchel A, de Haas V, Danen-van Oorschot AA, Fornerod M, Pieters R, Reinhardt D, Klusmann JH, van den Heuvel-Eibrink MM · Leukemia 2014
    used by let-7 microRNA family (12 HGNC loci) - the effector LIN28B blocks. CORRECTED IN-SESSION: the headline 'zero papers in KMT2A leukaemia' was a NAME-LIST ARTEFACT; searching MLL instead of KMT2A returns three, one of them directly on point, miR-9 — the most MLL-specific microRNA in AML, encoded at three separate loci nobody has disambiguated
100. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25267403
     Taspase1 cleaves MLL1 to activate cyclin E for HER2/neu breast tumorigenesis

     Dong Y, Van Tine BA, Oyama T, Wang PI, Cheng EH, Hsieh JJ · Cell Research 24(11):1354-1366 2014
     used by Lost from the KMT2A half: both taspase1 cleavage sites (D2666 and D2718) - the fusion is never processed, TASP1 (taspase1) - the protease that cuts KMT2A, and the timer the fusion escapes
101. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24530230
     MEAF6/PHF1 is a recurrent gene fusion in endometrial stromal sarcoma.

     Micci F, Gorunova L, Gatius S, Matias-Guiu X, et al. · Cancer Lett 2014
     used by Low-grade endometrial stromal sarcoma is a family of NuA4-acetyltransferase-to-Polycomb fusions, and that is why one of MBTD1's two fusions looks nothing like the other, MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma
102. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24479685
     Interferon-gamma induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages.

     Kuss M, Adamopoulou E, Kahle PJ · J Neurochem 2014
     used by LRRK2 - the AFF4 row is one of 78 hits on an in-vitro protein array, but the protein has a real AML literature that arrived through USP7 and interferon, not through the interactome
103. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24495227
     Human cell growth regulator Ly-1 antibody reactive homologue accelerates processing of preribosomal RNA.

     Miyazawa N, Yoshikawa H, Magae S, Ishikawa H, Izumikawa K, Terukina G, Suzuki A, Nakamura-Fujiyama S, Miura Y, Hayano T, Komatsu W, Isobe T, Takahashi N · Genes Cells 2014
     used by LYAR (Q9NX58) - a zinc-finger nucleolar growth regulator cloned from a T-cell leukaemia line, in six of seven MLL-fusion interactomes, and the one member of this block whose discovery system is the same lineage as the AP-MS host
104. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23959973
     Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma

     Dewaele B, Przybyl J, Quattrone A, et al. · International Journal of Cancer 2014
     used by MBTD1 - the H4K20me1/me2 reader inside NuA4/TIP60, the quiescence brake on adult haematopoietic stem cells, and the 3' partner of ZMYND11::MBTD1 whose methyl-lysine cage the fusion carries and does not use, MBTD1 is the effector-recruiting half of a leukaemia fusion and the addressing half of a sarcoma fusion while donating nearly all of itself to both - so the junction, not the parts, assigns the role, MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma, One stain, in the right order: H3K27me3 across a low-grade endometrial stromal sarcoma series first, and the three MBTD1::EZHIP blocks second
105. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24285434
     Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid tumors--molecular characterization shows genetic overlap with endometrial stromal sarcoma

     Antonescu CR, Sung YS, Chen CL, Zhang L, et al. · Genes Chromosomes Cancer 2014
     used by MEAF6 - a 191-residue subunit shared between the NuA4/TIP60 and MOZ/MORF acetyltransferase complexes, whose only two UniProt localisations both cite papers that are not localisation studies, PHF1 (PCL1) - the PRC2 accessory subunit whose Tudor domain reads H3K36me3, and the 3' acceptor shared by three different NuA4-donor fusions in two different tumour types
106. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25326802
     Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion

     Bruns I, Lucas D, Pinho S, Ahmed J, Lambert MP, Kunisaki Y, et al., Frenette PS · Nature Medicine 2014
     used by Megakaryocyte — the platelet factory whose loss causes the bruising that brings these children in, and which also holds stem cells still
107. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25326798
     Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells

     Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, et al., Li L · Nature Medicine 2014
     used by Megakaryocyte — the platelet factory whose loss causes the bruising that brings these children in, and which also holds stem cells still
108. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24604780
     PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration

     Baker CL, Walker M, Kajita S, Petkov PM, Paigen K · Genome Research 2014
     used by Meiotic recombination: hundreds of deliberate DNA breaks per cell, made by a topoisomerase relative, at sites chosen by a single zinc-finger protein
109. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24880125
     Degradation of AF1Q by chaperone-mediated autophagy.

     Li P, Ji M, Lu F, Zhang J, Li H, Cui T, et al. · Exp Cell Res 2014
     used by MLLT11 / AF1q — a 90-residue protein with no chromatin domain and no oligomerisation module, KMT2A partner in t(1;11)(q21;q23)
110. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24814343
     CFIm25 links alternative polyadenylation to glioblastoma tumour suppression.

     Masamha CP, Xia Z, Yang J, Albrecht TR, Li M, Shyu AB, Li W, Wagner EJ · Nature 2014
     used by NUDT21 / CFIm25 (O43809) - the CFIm subunit that picks poly(A) sites, in the pan-MLL-fusion core, and a paraspeckle protein
111. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24943837
     Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics.

     Buchwalter AL, Liang Y, Hetzer MW · Mol Biol Cell 2014
     used by NUP50 / Npap60 (Q9UKX7) - a MOBILE nuclear-basket nucleoporin in the pan-MLL-fusion core, and the evidence says basket, not nuclear envelope
112. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25145343
     NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report

     Ostronoff F, et al. · Blood 124(15):2400-2407 2014
     used by NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation
113. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     A Pilot Study of AMD3100 as a Sensitizing Agent in Myeloablative Allogeneic Blood and Marrow Transplantation for Chemotherapy Resistant Pediatric Acute Leukemia (Emory University, IRB00053638)

     · ClinicalTrials.gov 2014
     used by Plerixafor (AMD3100, Mozobil) - a licensed CXCR4 antagonist that has never been given to an infant with leukaemia, and whose only paediatric efficacy study failed, Registry sweep: is there any CXCR4-directed trial in KMT2A-rearranged or infant leukaemia? There is not, and the one paediatric attempt closed with a single patient
114. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 24488785
     The role of PML in hematopoietic and leukemic stem cell maintenance.

     Nakahara F, Weiss CN, Ito K · Int J Hematol 2014
     used by PML / TRIM19 (P29590) - the scaffold of PML nuclear bodies, co-purified with all seven MLL fusions, and never once studied as a KMT2A-fusion partner
115. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23958920
     Chemical genomic screening identifies LY294002 as a modulator of glucocorticoid resistance in MLL-rearranged infant ALL.

     Spijkers-Hagelstein JA, Pinhanços SS, Schneider P, Pieters R, Stam RW · Leukemia 2014
     used by Prednisolone - the active steroid, the drug every resistance experiment in this disease actually used, and the one given into the spinal fluid
116. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25056311
     Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins.

     Pradeepa MM, Grimes GR, et al. · Nucleic Acids Res 2014
     used by PSIP1 is a tumour suppressor in the lymphoid lineage next door: losing Psip1 ACCELERATES T-ALL in mice, while the same protein is a dependency in KMT2A-rearranged myeloid leukaemia, The result that runs the wrong way: in Psip1-null cells Hoxa and Hoxd expression goes UP, because Psip1 also recruits Bmi1 and Ctbp1
117. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24929677
     Recurrent read-through fusion transcripts in breast cancer

     Varley KE, Gertz J, Roberts BS, Myers RM, et al. · Breast Cancer Research and Treatment 2014
     used by Read-through (cis-SAGe) chimeras: most 'fusions' called from RNA-seq in childhood ALL are normal conjoined genes
118. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25474739
     Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

     Moriggi G, Nieto B, Dosil M · PLoS Genet 2014
     used by RRP12 (Q5JTH9) - a pre-40S export factor in six of seven MLL-fusion interactomes but NOT in the index fusion's, and the block's only member with a recessive human disease published in 2025
119. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24712655
     Nuclear import of SAMHD1 is mediated by a classical karyopherin α/β1 dependent pathway and confers sensitivity to VpxMAC induced ubiquitination and proteasomal degradation.

     Schaller T, Pollpeter D, Apolonia L, Goujon C, Malim MH · Retrovirology 2014
     used by SAMHD1 - the dNTP hydrolase that is the real biomarker behind the IMPDH story, and the reason the KMT2A framing of that story does not hold
120. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24449214
     SET-NUP214 is a recurrent γδ lineage-specific fusion transcript associated with corticosteroid/chemotherapy resistance in adult T-ALL.

     Ben Abdelali R, et al. · Blood 2014
     used by SET::NUP214 (TAF-Ibeta-NUP214, SET-CAN), cryptic del(9)(q34.11q34.13) - a HOXA-driving fusion of a histone chaperone to a nucleoporin, with no KMT2A and no menin-binding motif, SET::NUP214 adult T-ALL is gamma-delta-lineage-restricted and resistant to steroids and chemotherapy early - the same cell state CALM-AF10 occupies
121. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24509477
     Identification of functional cooperative mutations of SETD2 in human acute leukemia.

     Zhu X, He F, Zeng H, Ling S, Chen A, et al. · Nat Genet 2014
     used by SETD2 (Q9BYW2) - the H3K36 trimethyltransferase that binds all seven MLL fusions, and the only one of them with a published KMT2A::AFF1 dependency test
122. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24846945
     [Subcellular fluorescence localization analysis of all SAGA subunits in fission yeast (Schizosaccharomyces pombe)].

     Zhou X, Zhou N, Yu Y, Lv H · Yi Chuan 2014
     used by SGF29 — a SAGA reader with a Tudor pocket, intermediate essentiality, and the best unexploited profile in this beat
123. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24855208
     SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia

     Sasca D, Hahnel PS, Szybinski J, et al. · Blood 2014
     used by SIRT1 - not a fusion partner, the least required gene in KMT2A-rearranged lines, and the one target here where the direction of the drug is genuinely disputed
124. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25068121
     Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells.

     Rimmelé P, Bigarella CL, Liang R, Izac B, Dieguez-Gonzalez R, Barbet G, Donovan M, Brugnara C, Blander JM, Sinclair DA, Ghaffari S · Stem Cell Reports 2014
     used by SIRT1 - not a fusion partner, the least required gene in KMT2A-rearranged lines, and the one target here where the direction of the drug is genuinely disputed
125. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24847881
     SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer.

     Mazur PK, Reynoird N, et al. · Nature 2014
     used by SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
126. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25384085
     Anchored multiplex PCR for targeted next-generation sequencing

     Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, Lynch KD, Chen J, Robinson HE, Shim HS, Chmielecki J, Pao W, Engelman JA, Iafrate AJ, Le LP · Nature Medicine 2014
     used by Step 5: molecular confirmation and naming the partner
127. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24930734
     The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation.

     Nayak A, Viale-Bouroncle S, Morsczeck C, Muller S · Mol Cell 2014
     used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
128. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24927542
     DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin.

     Ayrapetov MK, Gursoy-Yuzugullu O, Xu C, Xu Y, et al. · Proceedings of the National Academy of Sciences 2014
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type, The H3K9me3 writer reaches the KMT2A anchor only through CTCF and only after the break - which would make this graph's CTCF arm and its H3K9 arm one arm, with CTCF upstream, and would make every resting-state H3K9me3 measurement at that element the wrong assay
129. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24754225
     Dynamics of WD-repeat containing proteins in SSU processome components.

     Wada K, Sato M, Araki N, Kumeta M, Hirai Y, et al. · Biochem Cell Biol 2014
     used by TBL3 / UTP13 (Q12788) - a UTP-B ribosome-biogenesis subunit in the pan-MLL-fusion core, whose loss in zebrafish severely reduces T cells and haematopoietic stem/progenitors, UTP18 / WDR50 (Q9Y5J1) - the SSU processome subunit that recruits the exosome helicase MTREX to rRNA fragments; in three MLL-fusion interactomes but not the index fusion's, and separately the subject of a 21-year-old IntAct curation error in this graph
130. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25064736
     The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.

     Larsen DH, Hari F, Clapperton JA, Gwerder M, Gutsche K, Altmeyer M, Jungmichel S, Toledo LI, Fink D, Rask MB, Grøfte M, Lukas C, Nielsen ML, Smerdon SJ, Lukas J, Stucki M · Nat Cell Biol 2014
     used by TCOF1 / treacle (Q13428) - the Treacher Collins nucleolar phosphoprotein in the MLL-fusion nucleolar block, the block's only link to rDNA damage signalling through NBS1, and the only member whose loss causes a named human developmental syndrome
131. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24507716
     Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation.

     Yang Y, McBride KM, Hensley S, Lu Y, Chedin F, Bedford MT · Molecular Cell 2014
     used by TDRD3 (Q9H7E2) - the reader the new H4R3me2a entry could not name, and it brings TOP3B to the MYC promoter and keeps R loops off it
132. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25136117
     Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells.

     Watanabe Y, Onodera A, Kanai U, Ichikawa T, Obata-Ninomiya K, Wada T, et al., Nakayama T · Proc Natl Acad Sci U S A 2014
     used by Th17 cell - the mature CD4 T-helper subset whose differentiation and maintenance require MENIN, which makes it the clearest published on-target normal-tissue liability of the menin interface
133. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 25186010
     Understanding the acetylome: translating targeted proteomics into meaningful physiology

     Kim SC, et al. (as cited); primary quotation from Am J Physiol Endocrinol Metab review · American Journal of Physiology - Cell/Endocrinology review, PMC4216940 2014
     used by The 2015 paper did not discover the KMT2A acetylation site - it inherited it from the 2009 Choudhary acetylome, which was run in a cell panel that includes MV4-11, a KMT2A::AFF1 line
134. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25416956
     A proteome-scale map of the human interactome network.

     Rolland T, Taşan M, Charloteaux B, et al., Vidal M · Cell 2014
     used by The four AFF4 two-hybrid partners are three rows of one screen, not three experiments - and in that same screen GOLGA2 has 249 partners while AFF4 has five
135. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25279926
     Inhibition of demethylases by GSK-J1/J4

     Heinemann B, Nielsen JM, Hudlebusch HR, ..., Helin K · Nature (Brief Communication Arising) 2014
     used by The KDM6 contradiction resolved one step: GSK-J4 inhibits UTX too, so it should ANTAGONISE a menin inhibitor - and nobody has combined them
136. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25456127
     Hematopoietic stem cells are intrinsically protected against MLL-ENL-mediated transformation.

     Ugale A, Norddahl GL, et al. · Cell reports 2014
     used by The neonatal window — the state in which an MLL fusion can transform, bounded at both ends
137. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25193880
     Effects of iron depletion on CALM-AF10 leukemias.

     Heath JL, et al. · Exp Hematol 2014
     used by The non-chromatin half: CALM-AF10 breaks the cell's iron intake and the cells are chelator-sensitive in vitro - but iron restriction did not extend survival in vivo (corrected 2026-09-21)
138. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25166220
     Shedding of NG2 by MMP-13 attenuates anoikis.

     Joo NE, Miao D, Bermúdez M, Stallcup WB, Kapila YL · DNA Cell Biol 2014
     used by The plasma membrane - the one compartment this graph targets with drugs and had never written down
139. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25141862
     Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo.

     Vlaming H, van Welsem T, de Graaf EL, Ontoso D, Altelaar AF, San-Segundo PA, Heck AJ, van Leeuwen F · EMBO Rep 2014
     used by The trans-histone crosstalk H2Bub → DOT1L → H3K79me: modulatory for me1, effectively required for me2/me3
140. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24832573
     TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition.

     Madsen DH, Szabo R, Molinolo AA et al · Biochemical Journal 2014
     used by TMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
141. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24463367
     Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells.

     Li Y, Hao H, Tzatzalos E, Lin RK, Doh S, Liu LF, et al. · Biol Open 2014
     used by TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically
142. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.reviewPMID 24787275
     A systematic description of MLL fusion gene formation

     Wright RL, Vaughan ATM · Critical Reviews in Oncology/Hematology 2014
     used by Transcription factories and Pol II clusters - no KMT2A::AFF1 imaging, condensate evidence for SEC and MLL-ENL, and 3D-FISH that actively contradicts the factory story for t(4;11)
143. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25368240
     High-density array comparative genomic hybridization detects novel copy number alterations in gastric adenocarcinoma.

     Seabra AD, Araujo TM, Mello Junior FA, et al. (11 authors; senior author Khayat AS) · Anticancer Res 2014
     used by Two of seven interactome read-queue partners should not get a gene entry, and the reasons are a pseudokinase with no nuclear pool and a membrane-skeleton protein whose two leukaemia hits are a gene-name artefact
144. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 25185265
     UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity.

     Bordeleau ME, Aucagne R, Chagraoui J, Girard S, Mayotte N, et al. · Blood 2014
     used by UBAP2L (Q14157) - a BMI1-interacting protein essential for haematopoietic stem cell activity, in the pan-MLL-fusion core, and a stress-granule nucleator recovered from NUCLEAR lysate
145. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24317448
     BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP.

     Morotti A, Panuzzo C, Crivellaro S, Pergolizzi B, Familiari U, Berger AH, Saglio G, Pandolfi PP · Leukemia 2014
     used by USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today
146. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 25301780
     CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing.

     Chan SL, Huppertz I, Yao C, Weng L, Moresco JJ, Yates JR 3rd, Ule J, Manley JL, Shi Y · Genes Dev 2014
     used by WDR33 (Q9C0J8) - the subunit that reads AAUAAA, in the pan-MLL-fusion core, and the plant homolog of which physically links 3' processing to H3K4 demethylation
147. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24985467
     A single point mutation in cyclin T1 eliminates binding to Hexim1, Cdk9 and RNA but not to AFF4 and enforces repression of HIV transcription.

     Kuzmina A, Verstraete N, Galker S, Maatook M, Bensaude O, Taube R · Retrovirology 2014
     used by What was searched, what came back empty, and what was read and not used - the P-TEFb reservoir beat's audit trail
148. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 25133424
     Menin determines K-RAS proliferative outputs in endocrine cells.

     Chamberlain CE, Scheel DW, McGlynn K, Kim H, Miyatsuka T, Wang J, et al. · Journal of Clinical Investigation 2014
     used by Why endocrine tumours do not carry KRAS mutations: menin blocks the proliferative arm of RAS
149. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24413322
     WTAP is a novel oncogenic protein in acute myeloid leukemia

     Bansal H, et al. · Leukemia 2014
     used by WTAP — an oncogenic m6A writer subunit in AML with ZERO records against MLL or KMT2A over six aliases
150. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24590075
     ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression

     Wen H, Li Y, Xi Y, Jiang S, Stratton S, Peng D, et al. · Nature 2014
     used by ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11, ZMYND11::MBTD1 is the KMT2A-fusion architecture assembled from different parts - and the part it throws away is a direct physical brake on KMT2A itself
151. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23915195
     Recurrent translocation (10;17)(p15;q21) in acute poorly differentiated myeloid leukemia likely results in ZMYND11-MBTD1 fusion

     De Braekeleer E, Auffret R, Douet-Guilbert N, et al. · Leukemia & Lymphoma 2014
     used by ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
152. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23412334
     Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia.

     Wang E, Kawaoka S, Yu M, Shi J, Ni T, Yang W, Zhu J, Roeder RG, Vakoc CR · Proc Natl Acad Sci U S A 2013
     used by "Diverse models of MLL-rearranged leukaemia" is one mouse cell line: the RNF20 H2Bub requirement resolves to murine RN2 (MLL-AF9/NrasG12D), H2BK120ub (H2Bub1) — the ubiquitin tag on histone H2B that licenses H3K79 methylation, and the mark this graph was missing, Nobody knows which way to push H2Bub in this disease, and the only available compound pushes it upward, RNF20 (BRE1A) — the H2B ubiquitin ligase that MLL-rearranged leukaemia needs, and that DepMap says every other cancer line needs just as much
153. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     The histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia (GSE43725)

     GEO submitters · NCBI Gene Expression Omnibus 2013
     used by "Diverse models of MLL-rearranged leukaemia" is one mouse cell line: the RNF20 H2Bub requirement resolves to murine RN2 (MLL-AF9/NrasG12D)
154. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23782611
     GAT: a simulation framework for testing the association of genomic intervals

     Heger A, Webber C, Goodson M, Ponting CP, Lunter G · Bioinformatics 29:2046-2048 2013
     used by A cohort median is a summary of many nulls and the null of none of them, A Jaccard index is not a result until its null knows that active promoters cluster, The 0.069 chance floor quoted beside the 0.400 same-patient Jaccard is the cohort MEDIAN's null, and this pair's own floor is 0.267, The two beats' opposite answers are produced by the calling rule, not by the promoter universe: three universes give one answer, two rules give two
155. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24121163
     The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.

     · Blood Cancer Journal 2013
     used by A junction-specific monoclonal antibody against a paediatric leukaemia fusion oncoprotein exists: clone TEL 6F2, raised against a 12-mer spanning the ETV6::RUNX1 fusion site and used for genome-wide ChIP, Raise a KMT2A::AFF1 junction-specific monoclonal by the published TEL 6F2 protocol - rat immunisation with a junction peptide, ELISA and western screen, then a ChIP test against the wild-type-parent controls that the ETV6::RUNX1 campaign never ran
156. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23224434
     The tumor suppressor protein menin inhibits NF-κB-mediated transactivation through recruitment of Sirt1 in hepatocellular carcinoma.

     Gang D, Hongwei H, Hedai L, Ming Z, Qian H, Zhijun L · Mol Biol Rep 2013
     used by A menin inhibitor may release RELA from menin's restraint — and released RELA is what keeps MLL fusions on chromatin. Prior 0.20, Menin represses NF-kB transactivation — through a mapped central region, a SIRT1 cofactor, and an RPA2 off-switch, in every tissue except the one this project cares about, RELA (p65) — menin binds it and represses it, and it is required to keep MLL oncoproteins on chromatin
157. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24054986
     Epigenetic roles of MLL oncoproteins are dependent on NF-κB.

     Kuo HP, Wang Z, Lee DF, Iwasaki M, Duque-Afonso J, Wong SH, Lin CH, Figueroa ME, Su J, Lemischka IR, Cleary ML · Cancer Cell 2013
     used by A menin inhibitor may release RELA from menin's restraint — and released RELA is what keeps MLL fusions on chromatin. Prior 0.20, Blocking IKK/NF-kB in an infant is removing the switch every immune cell runs on — and the class has already failed clinically on exactly that, Bortezomib is called an NF-kB inhibitor, and in MLL leukaemia it does two different things in two lineages — neither of which is reliably NF-kB in the lymphoid one, Canonical versus non-canonical NF-kB in KMT2A-rearranged leukaemia — the two arms have opposite signs, and the two papers usually read as contradicting each other actually agree, CHUK (IKK-alpha) — the only kinase that sits in BOTH NF-kB arms, which makes it the one subunit whose inhibition has an ambiguous sign in this disease, Combine an IKK inhibitor with a clinical menin inhibitor in a KMT2A::AFF1 B-ALL line, and read out fusion OCCUPANCY rather than viability, Every upstream NF-kB component this beat enumerated, with its query, its count, and why it did or did not get an entry, IKBKB (IKK-beta) — the kinase whose knockdown tracks MLL-leukaemia growth most tightly, and whose inhibitors have failed clinically for a reason, IKBKG (NEMO) — the scaffold that makes the canonical complex a complex, and a symbol that returns ZERO records in this disease, IKK inhibition and menin inhibition evict the fusion from chromatin by routes that do not share a node, so they should be additive — and the same reasoning predicts that a menin inhibitor alone partially defeats itself. Prior 0.30, IKK/NF-kB retains MLL on chromatin — BOTH the fusion and wild-type MLL, at two promoters, in mouse myeloid AML, and it is occupancy loss rather than protein loss, IL-1/IRAK1/4 — the receptor-proximal input the MLL screen actually pointed at, with an Il1r1 knockout in MLL-AF9 mice and an inhibitor that spares normal stem cells, NFKB1 (p105/p50) — the only menin-NF-kB subunit with a co-immunoprecipitation, and the arm the MLL leukaemia data points at, NFKB2 (p100/p52) — menin binds the non-canonical subunit too, and activating that arm SUPPRESSES MLL-AF9 leukaemia, NFKBIA (IkB-alpha) — the switch itself. This graph has entries for everything the switch controls and none for the switch, RELA (p65) — menin binds it and represses it, and it is required to keep MLL oncoproteins on chromatin, The IKK complex — the unit the eviction experiment actually resolves, because the chemistry that produced the result cannot see the subunits, The NF-kB story in KMT2A-rearranged leukaemia is a myeloid story, and the lymphoid half is not a weaker version of it — it is a different subject, TNF — the only NF-kB-activating ligand with real KMT2A::AFF1 B-ALL evidence, and the evidence says the blasts are RESISTANT to it
158. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24285714
     Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.

     Shi J, Whyte WA, Zepeda-Mendoza CJ, Milazzo JP, Shen C, Roe JS, et al. · Genes Dev 2013
     used by A noncoding element has no HGNC symbol, so every rule in this brief for resolving an identifier fails on it - worked on the one MYC enhancer that matters, ARID1A (BAF250A) - required in the MLL-AF9 screen, present at the Myc enhancers, and flat in every selectivity measure, BAF does not work where the fusion works: most direct MLL-AF9 targets do not respond to Brg1 loss, and the SWI/SNF address is a distal MYC enhancer cluster 1.7 Mb away, BAF inhibition against the menin axis: on the evidence it is a complement, not an alternative - and the case rests on one laboratory, BENC - the MYC blood enhancer cluster 1.7 Mb downstream, required for MLL-AF9 leukaemia maintenance, and named in zero entries of this graph until now, DPF2 (BAF45D) - a cBAF-specific reader required in MLL-AF9 cells, with one PubMed record in this disease and no selectivity signal, How BAF maintains KMT2A-rearranged leukaemia: it holds the blast undifferentiated, and it does so in other leukaemias too, In inv(16), disrupting the fusion interface swaps BRG1 for RING1B at three MYC enhancers - the cleanest version anywhere of the experiment nobody has run on menin, Is BENC even on in the disease this project is about? A module-resolved accessibility and deletion map in KMT2A::AFF1 B-lineage cells, Is MYC the node? Two papers, the same MLL-AF9 model, opposite answers - and the second one failed to rescue, Menin inhibition recruits PRC1 to the BENC MYC enhancer cluster and evicts BRG1, exactly as CBFbeta-SMMHC inhibition does in inv(16), SMARCA2 (BRM) - the paralogue nobody measured, and the reason a DepMap rank cannot predict what a BRG1/BRM inhibitor does, SMARCA4 (BRG1) - a tumour suppressor by mutation and a maintenance requirement by knockdown, and in KMT2A-rearranged lines the dependency data say it is not selective at all, SMARCB1 (BAF47/INI1/SNF5) - zero entries, zero mentions and, on the evidence, correctly so: it is lost in primary AML rather than required, SMARCD1 (BAF60A) - rank 59 of 17,728, survives the lineage split, and had never been named in this graph or studied in this disease, SMARCD2 (BAF60B) - named in one KMT2A paper in the whole of PubMed, and the dependency it carries is myeloid identity, not the rearrangement, The MYC contradiction can be advanced but not closed: the enhancer is independently validated, the SWI/SNF route is not, and the two papers never measured the same thing, The SWI/SNF dependency in KMT2A-rearranged leukaemia belongs to ncBAF, not to canonical BAF - and the drug in the clinic is aimed at the wrong module, When MYC falls after a menin inhibitor, there are three mechanisms it could be, and no published experiment separates them
159. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23487024
     A CALM-derived nuclear export signal is essential for CALM-AF10-mediated leukemogenesis.

     Conway AE, et al. · Blood 2013
     used by A ten-residue export signal is the 5' partner's whole contribution - and the field disagrees about which direction it pushes, CALM-AF10 is predominantly cytoplasmic in transfected non-haematopoietic cells - and NUCLEAR in leukaemia cells (title corrected 2026-09-21; the five systems are five instances of one design), CALM-AF10 reaches DOT1L through exactly the same OM-LZ interface as KMT2A::MLLT10 - the recruitment transfers, the addressing does not, CALM-AF10 strips H3K79 methylation from the rest of the genome while adding it at HOXA - one fusion, two opposite effects on the same mark, Export or docking? A locus-resolved H3K79me2 ChIP under an XPO1 inhibitor separates the two CALM-AF10 models, and it has never been run, PICALM (CALM) - the clathrin-assembly adaptor that is the 5' partner of CALM::AF10, PICALM / CALM - domain architecture, residue coordinates, and which parts the fusion keeps, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A, The focal half: H3K79 hypermethylation at the HOXA cluster and MEIS1 - but which cluster member differs between CALM-AF10 and MLL-AF10, Where the break falls, and the three incompatible numbering frames that make it easy to get wrong
160. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23990460
     Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia.

     Risner LE, Kuntimaddi A, Lokken AA, et al. · J Biol Chem 2013
     used by A tighter CXXC domain fails and a weaker one works: affinity rank does not predict function in the MLL-AF9 swap series, CORRECTED: two of eleven CXXC readers HAVE been measured alongside a KMT2A fusion, and the result supports the menin-interface hypothesis, CXXC1 (CFP1) - a CpG-reading COMPASS subunit that binds MLL1 and recruits it to HoxA7, and whose CXXC domain cannot substitute for KMT2A's in a fusion, DNMT1 - the antagonist: its CXXC domain reads unmethylated CpG in order to STOP methylation, and it is the only heterologous CXXC that runs an MLL-AF9 leukaemia, Interactome round 5: 42 queries, 13 entries written, 9 candidates rejected with counts, and four alias failures of four different kinds, Is the CpG address a contested resource? On current evidence, no - and the beat that went looking says so, MBD1 - one protein with a methyl-CpG reader and three CXXC fingers, only the third of which binds unmethylated CpG, and whose CXXC fails the MLL-AF9 swap, Phase-2 dossier: the CXXC-DNA interface - two structures, a genetically validated requirement, and a selectivity problem that decides everything, Re-founding the address argument: the CXXC domain cannot specify a location at any affinity, and a tighter one would be worse, TET1 (LCX / CXXC6) - a CXXC reader that is also a KMT2A fusion partner, and whose leukaemic fusion throws its own CXXC domain away, The CXXC-DNA affinity is a ten-point ladder from 44 uM to 33 nM, not two numbers 1,300-fold apart, and every step but the last is under 5.5-fold, The human CXXC/CpG-reading family is exactly twelve proteins, and TET2 is not one of them, Two entries record zero chemical matter against the CXXC-DNA interface. There is one: dimethyl fumarate, IC50 about 1 uM, and it is already an approved drug
161. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23539624
     Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription.

     Bartholomeeusen K, Fujinaga K, Xiang Y, Peterlin BM · The Journal of Biological Chemistry 288(20):14400-14407 2013
     used by Acetylation is a cycle, not a mark - and this graph holds one complete cycle, on a residue the fusion throws away, HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less, Measure the free-versus-7SK-bound P-TEFb split in KMT2A::AFF1 cells - the experiment this whole beat turns on, which has never been done, Raising HEXIM1 to brake the fusion's output without touching the fusion - one supporting experiment, one chemical series, and no therapeutic window, Vorinostat (SAHA) - the only HDAC inhibitor given to newly diagnosed infants with ALL, in a 50-patient trial whose endpoint was tolerability and which reported four treatment-related deaths, all infectious
162. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23579270
     Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.

     Yang YJ, Song TY, Park J, Lee J, Lim J, Jang H, Kim YN, Yang JH, Song Y, Choi A, Lee HY, Jo CH, Han JW, Kim ST, Youn HD, Cho EJ · Cell Death Dis 2013
     used by ADJUDICATION: the SvID and the gamma-H2A.X motif are OVERLAPPING BUT NOT THE SAME SURFACE - and the premise that made the question urgent, that the SvID is distinct from the MLL cavity, is FALSE at the SvID's own boundary, SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type, The menin acidic shelf, Glu366-Asp370-Val371: the counter-charge that MBM2 binds, resolved in 3U88 after all - and the one patch where the drug pocket, the SvID and the gamma-H2A.X motif all touch, The SvID, menin 360-445: a truncation boundary the field reads as a domain, whose functional residues D418 and W436 are 10-20 A from every menin drug - but whose first ten residues ARE the drug pocket, The two co-IPs that settle whether menin's SUV39H1 window and its gamma-H2A.X motif are one surface: swap each laboratory's construct into the other's assay
163. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB entry 2LM0 — Solution structure of the AF4-AF9 complex

     Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH · RCSB Protein Data Bank 2013
     used by AFF1 / AF4 — domain architecture and residue coordinates, AFF1-AFF4 heterodimerisation through the C-terminal homology domain: the one SEC interface KMT2A::AFF1 certainly keeps, defined by a 2.2 A structure of the wrong subunit, The AFF-family N-terminus on cyclin T1: Kd 10 nM, a 2.94 A crystal, and every number in it measured on AFF4 rather than on AFF1, The ENL AHD to AFF1 contact: asserted throughout this graph, structurally unsolved, and represented only by an AF9 chimera measured at KD 0.17 nM
164. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23260655
     Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding

     Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH · Structure 21:176-183 2013
     used by AFF1 / AF4 — domain architecture and residue coordinates, AFF1 AF4_int motif to AF9/ENL AHD: the index fusion's only documented elongation interface, and it competes with DOT1L, AFF1 reaches P-TEFb only through AFF4, and the index fusion's elongation phenotype is therefore a claim about AFF4 availability, BCOR, not CBX8, is the AHD contact MLL-AF9 cannot lose - and the same two partners bind ENL far more tightly than AF9, Import class 2: AHD-dependent mechanism, which cannot transfer because KMT2A::AFF1 has no AHD, KMT2A::AFF1 has no mapped interface to DOT1L: it lacks both structurally defined recruitment modules, and the one complex-level route claimed for it is contested by reconstitution, KMT2B, AFF2, AFF3, AFF4 and ENL carry most of the contact residues of the two interfaces the fusion keeps (menin-KMT2A and AF9-AFF1), so a substitute is structurally possible and selectivity cannot be read from either surface; at the menin side KMT2B differs at W7, Measure the one number the whole YEATS-selectivity argument turns on: what fraction of ENL and of AF9 is in SEC, in SEC-L2, in SEC-L3 and free — with an exchange control, because the question may not be well posed, The CRISPR-ChIP H3K79 partition is a mouse MLL-AF9 result: resolved from GEO after the full text proved unreachable, The ENL AHD to AFF1 contact: asserted throughout this graph, structurally unsolved, and represented only by an AF9 chimera measured at KD 0.17 nM, The index fusion's 3' partner has ONE observed binary interaction in IntAct and forty-two residues of solved structure - every SEC contact attributed to AFF1 is an AFF4 result wearing AFF1's name, The KMT2A::MLLT3 chimeric protein: what survives the join on each side, in residue numbers - and the four AF9 modules that do not, The retained AF9 surface in residue detail: one disordered 70-mer, three DOT1L sites, two of them high-affinity and simultaneously occupiable, The transfer rule: which MLL-AF9 results can be carried into t(11;19) and t(4;11), and which are statements about a protein missing a reading module, Two surfaces, two jobs: the AHD picks the scaffold and the YEATS pocket reads the histone — so a YEATS ligand cannot ask which of the three SEC-family complexes it is disabling
165. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23602568
     The protein interaction landscape of the human CMGC kinase group.

     Varjosalo M, Keskitalo S, Van Drogen A, Nurkkala H, Vichalkovski A, Aebersold R, Gstaiger M · Cell Rep 2013
     used by AFF4-CDK15: AFF4 is prey in a systematic CMGC-kinase TAP interactome - a kinase adjacent to the complex CDK9 works in, and nobody has followed it up
166. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23995757
     Regulation of transcription by the MLL2 complex and MLL complex-associated AKAP95.

     Jiang H, Lu X, Shimada M, Dou Y, Tang Z, Roeder RG · Nat Struct Mol Biol 2013
     used by AKAP8 (AKAP95) - the only nuclear A-kinase anchoring protein, and the one that turned out to be required for MLL-rearranged leukaemia, AKAP95 directly enhances H3K4 mono-, di- and tri-methylation - by the KMT2B complex, and ONLY by the KMT2B complex; the paper's own discussion says the MLL1/KMT2A case was never tested, AKAP95 is phenotypically silent at steady state and required only when a cell is changing state - the same shape in ATRA differentiation and in MLL-AF9 transformation, thirteen years apart, AKAP95 reaches this disease by two separate routes - through WRAD/DPY30 and through the retained KMT2A fragment - and only the second one survives the fusion, AKAP95-DPY30: a direct contact whose binding determinant two groups map to OPPOSITE ends of AKAP95, and neither has been structurally resolved, AKAP95's requirement in KMT2A-rearranged leukaemia runs entirely through IDR co-condensation with the retained fragment, and not at all through DPY30 - so a DPY30-binding-dead AKAP95 will fully rescue, AKAP95's subnuclear addresses - nuclear matrix, nucleolus, and dynamic foci - and the finding that the famous one is the one its MLL-linked function does not need, Eight claims this corpus carries from PMID 23995757, checked one at a time against the full text: five confirmed, one scope-limited, one materially different, one not in the paper at all, KMT2A-AKAP8 (AKAP95): graded 'prey-only' by this project, and it is a direct positive modulator of MLL H3K4 methyltransferase activity from a dedicated MLL paper - ADMITTED, No published experiment combines an AKAP95 perturbation with any menin or DOT1L inhibitor - bounded by an enumerated 92-record literature, not by a keyword zero, Separate AKAP95's two routes into the KMT2A axis - starting with one transfection that re-reads a thirteen-year-old control, The bait/prey grade this project uses to triage the interactome systematically discards its strongest evidence, because the strongest methods have no bait
167. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23352661
     RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.

     Wilkinson AC, Ballabio E, Geng H, et al. · Cell Rep 2013
     used by An anti-MLL-C antibody in a t(4;11) cell is looking at two proteins at once, Forty-five percent of t(4;11) patients express a KMT2A fusion transcript that keeps the whole WRAD interface, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum, Reciprocal status is a different fact depending on whether you assay DNA or RNA, and the whole prognostic literature is RNA, RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11), What the reciprocal product assembles: P-TEFb, an H3K4 methyltransferase, an H3K79 methyltransferase, an arginine methyltransferase and an acetyltransferase
168. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24063430
     Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

     Nordlund J, Backlin CL, Wahlberg P, et al. (Syvanen AC, senior author) · Genome Biology 14(9):r105 2013
     used by Analysis (runnable): does the infant methylome predict HOXA status once age and breakpoint are controlled?, The KMT2A-r DNA methylation signature — focal hypermethylation, no global hypomethylation, and a hypomethylating agent that did not help
169. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23983156
     Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials

     Berry SM, Broglio KR, Groshen S, Berry DA · Clinical Trials 2013
     used by Basket and umbrella designs: pooling rare fusions into one trial, Bayesian borrowing: how many infants a prior is worth, and when it lies
170. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23523425
     Structure of the polycomb group protein PCGF1 in complex with BCOR reveals basis for binding selectivity of PCGF homologs

     Junco SE, Wang R, Gaipa JC, Taylor AB, Schirf V, Gearhart MD, Bardwell VJ, Demeler B, Hart PJ, Kim CA · Structure 21(4):665-71 2013
     used by BCORL1 — the BCOR paralogue that is in the only crystal structure of the PRC1.1 core, and is the one PRC1.1 subunit nobody has tested in KMT2A-rearranged leukaemia, PCGF1 — the PRC1.1 scaffold whose LOSS causes menin-inhibitor resistance, so it is a restraint on the leukaemia rather than a dependency of it
171. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24180494
     A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias

     Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H · N Engl J Med 2013
     used by BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11)
172. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23138183
     Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l.

     Chen L, et al. · Leukemia 2013
     used by Bite-back: a DOT1L inhibitor in CALM-AF10 deepens a genome-wide H3K79 deficit that already causes chromosome breaks, CALM-AF10 strips H3K79 methylation from the rest of the genome while adding it at HOXA - one fusion, two opposite effects on the same mark, CALM-AF10 was meant to separate the menin axis from the HOXA programme - and the indirect evidence has now turned against separability, because KMT2A-free HOXA lesions keep proving menin-DEPENDENT, Hypothesis: the haem and iron dependency of KMT2A-rearranged lines is monocytic physiology, not fusion biology — and the panel cannot tell us either way, KMT2A::MLLT10 (MLL-AF10), t(10;11)(p12;q23), Losing the AF10 PZP reader is not a missing function - it is a removed brake, and putting it back cures the fusion, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A, Run the menin inhibitor against CALM-AF10 next to a KMT2A-rearranged control - the missing two-week experiment, Settle the monocytic confound isogenically: degrade the fusion, read haem-gene dependency before lineage has time to move, The focal half: H3K79 hypermethylation at the HOXA cluster and MEIS1 - but which cluster member differs between CALM-AF10 and MLL-AF10, The monocytic confound is worse than recorded: two of the six rearranged lines are one patient, and the four-line control group contains a HOXA-driven fusion and two NPM1c/myelomonocytic lines, Why this one rare leukaemia was thought to decide an argument about a drug used in a commoner one - and why it decides less than the title says (corrected 2026-09-21)
173. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23948297
     A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis

     Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schafer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zochbauer-Muller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl R, Busslinger M, Malumbres M, Sexl V · Cancer Cell 24:167-181 2013
     used by BMI1, CDKN2A and CDK6 are one circuit, not three genes - and in KMT2A-rearranged disease it has a loop nobody has measured, CDK6 - the kinase the KMT2A-r rationale actually rests on, and the pan-essentiality flag and the selectivity are both true
174. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23432364
     The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia

     Emerenciano M, Meyer C, Mansur MB, Marschalek R, Pombo-de-Oliveira MS · British Journal of Haematology 2013
     used by Breakpoint anatomy, and an audit of the prognosis claim, Do different breaks give different biology? A verdict on partner identity vs breakpoint position, Each partner prefers a different KMT2A exon: partner-specific break position in 3,401 patients, Hypothesis: the KMT2A genomic breakpoint carries prognostic information that the field has been sitting on for twenty years, KMT2A exon 11 / intron 11 breakpoints (BCR subregion C): the infant, HOXA-low, topoisomerase-II-associated break, KMT2A intron 9 / exon 9 breakpoints (BCR subregion A): the HOXA-high, older-patient break
175. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23769972
     Discovering regulators of centriole biogenesis through siRNA-based functional genomics in human cells.

     Balestra FR, Strnad P, Flueckiger I et al · Developmental Cell 2013
     used by C2CD3 - the centriole-elongation regulator fused to KMT2A exon 8 in an MPNST, predicted OUT OF FRAME, and the partner whose RefSeq transcript is 390 residues shorter than UniProt's canonical
176. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23531517
     NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern

     de Rooij JDE, Hollink IHIM, Arentsen-Peters STCJM, van Galen JF, Berna Beverloo H, Baruchel A, Trka J, Reinhardt D, Sonneveld E, Zimmermann M, Alonzo TA, Pieters R, Meshinchi S, van den Heuvel-Eibrink MM, Zwaan CM · Leukemia 2013
     used by CBFA2T3::GLIS2, inv(16)(p13.3q24.3), NUP98::KDM5A (NUP98-JARID1A), t(11;12)(p15;p13)
177. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24055056
     Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1.

     Ben-Ami O, Friedman D, Leshkowitz D, et al. · Cell Reports 2013
     used by CBFB::MYH11 (CBFbeta-SMMHC), inv(16)(p13;q22), Hypothesis — the menin lesson generalises: every non-enzymatic fusion has an obligate partner interface that is more druggable than the fusion, Mechanism class 2 — transcription-factor corruption (RUNX1::RUNX1T1, PML::RARA, ETV6::RUNX1, CBFB::MYH11) — a balance, not a pure dominant negative
178. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23900238
     MLL fusion protein-driven AML is selectively inhibited by targeted disruption of the MLL-PAFc interaction.

     Muntean AG, Chen W, Jones M, Granowicz EM, Maillard I, Hess JL · Blood 2013
     used by CDC73 / parafibromin — the PAF1C subunit that was genetically tested, and a second tumour suppressor required by the fusion, PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein
179. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23471103
     The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat.

     Schulze-Gahmen U, Upton H, Birnberg A, Bao K, Chou S, Krogan NJ, Zhou Q, Alber T · Elife 2013
     used by CDK9 - the kinase the whole SEC story runs through, which this graph held only as half of a two-protein summary entry, P-TEFb (CDK9 + cyclin T1) — the deepest dependency and the clearest therapeutic-index wall in the interactome, The AFF-family N-terminus on cyclin T1: Kd 10 nM, a 2.94 A crystal, and every number in it measured on AFF4 rather than on AFF1, The fusion begins at AFF1 residue 347 and the cyclin T1-binding sequence ends at 308, so KMT2A::AFF1 is the one AFF-family protein that cannot enter the reservoir
180. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24054362
     Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma

     Lee TH, Jang AS, Park JS, Kim TH, Choi YS, Shin HR, et al., Park CS · Annals of Allergy, Asthma and Immunology 2013
     used by Cell identities considered and not written: what the search actually returned for basophils, mast cells, eosinophils, NK cells and the rest
181. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23680298
     Cell cycle-dependent localization of CHK2 at centrosomes during mitosis.

     Chouinard G, Clément I, Lafontaine J, Rodier F, Schmitt E · Cell Div 2013
     used by CHEK2 (CHK2) - named in every combination mechanism here and measured on its own in none of them
182. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23434755
     Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches

     Ding L, Morrison SJ · Nature 2013
     used by CXCL12 (SDF-1) - the marrow retention chemokine this graph already had a mechanism entry for and no entry for the protein, CXCL12-CXCR4 retention — the axis everyone calls the niche dependency, and the CRISPR screen that says the ligand is not required, The age of the marrow, not only the age of the cell, decides whether MLL-rearranged leukaemia comes out myeloid or lymphoid, The endosteal niche — the bone surface, where leukaemia-initiating cells were imaged homing and dividing symmetrically
183. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23294096
     MLL-rearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism

     Sison EA, Rau RE, McIntyre E, Li L, Small D, Brown P · Br J Haematol 2013
     used by CXCR4 - named in eighteen entries of this graph with no entry of its own, and the one niche molecule with a drug, a paediatric trial and a direct KMT2A-r experiment, Niche biology HAS been measured in KMT2A-rearranged disease - but in the index fusion itself there is essentially one marrow-niche molecular experiment, from 2011, Plerixafor (AMD3100, Mozobil) - a licensed CXCR4 antagonist that has never been given to an infant with leukaemia, and whose only paediatric efficacy study failed, Where KMT2A-rearranged leukemia physically sits — marrow niche, CNS, blood, liver/spleen and skin
184. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23563267
     Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.

     Ko M, An J, et al. · Nature 2013
     used by CXXC4 (IDAX) - TET2's CXXC domain, sitting on a separate gene after an evolutionary inversion, and annotated cytoplasmic only by similarity, TET2 is NOT a CXXC protein - its CXXC domain is a separate gene, and it is DEPLETED in KMT2A-rearranged AML rather than enriched, The human CXXC/CpG-reading family is exactly twelve proteins, and TET2 is not one of them
185. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23690950
     Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules.

     Liu N, Wang M, et al. · PLoS One 2013
     used by CXXC4 (IDAX) - TET2's CXXC domain, sitting on a separate gene after an evolutionary inversion, and annotated cytoplasmic only by similarity, TET3 - the CXXC reader whose domain prefers 5-carboxylcytosine, and the only CXXC-family gene ever found mutated in a KMT2A-rearranged cohort, The human CXXC/CpG-reading family is exactly twelve proteins, and TET2 is not one of them
186. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23988457
     CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia.

     Astori A, Fredly H, et al. · Oncotarget 2013
     used by CXXC5 (RINF) - the one CXXC reader measurably down-regulated in KMT2A-rearranged AML, which is the only direction-of-change any family member has in this disease
187. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23334362
     Src kinase-induced phosphorylation of annexin A2 mediates glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia.

     Spijkers-Hagelstein JA, Mimoso Pinhanços S, Schneider P, Pieters R, Stam RW · Leukemia 2013
     used by Dexamethasone - the steroid an infant is actually on for most of the protocol, and the one with a high-certainty neurodevelopmental signal in babies, Prednisolone - the active steroid, the drug every resistance experiment in this disease actually used, and the one given into the spinal fluid
188. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23648481
     MEN1 is a melanoma tumor suppressor that preserves genomic integrity by stimulating transcription of genes that promote homologous recombination-directed DNA repair.

     Fang M, et al. · Mol Cell Biol 2013
     used by DNA damage raises menin levels through ATM/ATR phosphorylation, and the residue has never been mapped
189. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23801631
     Potent inhibition of DOT1L as treatment of MLL-fusion leukemia

     Daigle SR, Olhava EJ, Therkelsen CA, et al. · Blood 2013
     used by DOT1L — the target where excellent chemistry met an indirect interaction, In SEM, H3K4me3 responds to menin displacement the way a partially redundant mark should: selectively at menin-bound sites, by about a quarter, and not at all under a DOT1L inhibitor - which bounds how much of a menin inhibitor's lethality H3K4me3 can be carrying, In SEM, the infant-derived KMT2A::AFF1 line, VTP-50469 lowers H3K4me3 at menin-bound sites by 23% relative to H3K4me3-matched menin-free sites (95% CI 13-33%), while the DOT1L inhibitor EPZ-5676 changes it by 1% (CI -4 to +6%), Step 4 — The histone mark: DOT1L and H3K79me2/3 at fusion target genes (and why global expression barely moves)
190. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22469984
     The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia.

     Shi J, Wang E, Zuber J, Rappaport A, Taylor M, Johns C, et al. · Oncogene 2013
     used by EED - the PRC2 subunit this disease actually needs, with drugs in the clinic and zero leukaemia studies, EZH1 - the paralogue that makes the approved EZH2 drug the wrong drug for this disease, Polycomb in KMT2A-r leukemia — core PRC2 required, EZH2 and BMI1 dispensable, and CBX8 acting outside its repressive role, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, SUZ12 - the scaffold that holds PRC2 together and decides which PRC2 it is, required in this disease and studied in it exactly once
191. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23932780
     The little elongation complex functions at initiation and elongation phases of snRNA gene transcription.

     Hu D, Smith ER, Garruss AS, Mohaghegh N, Varberg JM, Lin C, Jackson J, Gao X, Saraf A, Florens L, Washburn MP, Eissenberg JC · Mol Cell 2013
     used by ELL is in Cajal bodies - or nuclear speckles, depending which paper you read - and the MLL-ELL fusion empties them, ICE1 — the 2,266-residue scaffold of the little elongation complex, the subunit that acts at initiation, and zero papers connecting it to leukaemia of any kind, ICE2 — the fourth LEC subunit, the one with no assigned step, no structure, and no leukaemia literature, ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
192. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23327922
     Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia

     Diffner E, Beck D, Gudgin E, Thoms JA, Knezevic K, Pridans C, Foster S, Goode D, et al. · Blood 121:2289-2300 2013
     used by ERG - a heptad stem-cell transcription factor whose 15 mentions in this graph are mostly about OTHER diseases, and whose best-established role in B-ALL is loss of function, not cooperation
193. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24107994
     Arteriolar niches maintain haematopoietic stem cell quiescence

     Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, et al. · Nature 2013
     used by Every niche-disrupting drug strips the patient's own stem cells of the same shelter — the bite-back that applies to the whole beat, NG2+ periarteriolar pericyte — the cell that holds blood stem cells asleep, and the one MLL-AF9 leukaemia destroys, The bone-marrow niche — the address a blood stem cell lives at, which 26 entries in this graph invoke and none had defined, The perivascular and sinusoidal niche — where the functional evidence actually sits, and where the marrow is genuinely hypoxic
194. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23302800
     Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance

     Das Thakur M, Salangsang F, Landman AS, et al. · Nature 2013
     used by Experiment: does a MEN1 resistance mutant pay a price when the drug is not there? The competition assay nobody has run, Hypothesis: adaptive scheduling of menin inhibitors will fail, because MEN1 resistance mutations probably cost the cell nothing, Hypothesis: menin-inhibitor effect is hysteretic — the program collapses faster than it recovers — so intermittent dosing can hold efficacy at much lower cumulative exposure
195. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23349306
     The trithorax protein partner menin acts in tandem with EZH2 to suppress C/EBPα and differentiation in MLL-AF9 leukemia.

     Thiel AT, Feng Z, Pant DK, Chodosh LA, Hua X · Haematologica 2013
     used by EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off, Measure H3K27me3 after a menin inhibitor - the free pharmacodynamic nobody has read, and the one experiment that separates two mechanisms, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, PRC2 is the fusion's repressive arm, recruited through menin, and the index disease's version of it runs to HDAC7, Trithorax against Polycomb at HOXA: the textbook antagonism, and the two ways this disease breaks it
196. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23908472
     Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells

     Li BE, Gan T, Meyerson M, Rabbitts TH, Ernst P · Blood 2013
     used by Fiduciary conflict of interest — law does not remove a conflicted agent, it separates the mandates, MEN1 / menin — the adaptor the fusion cannot work without, Patricia Ernst (University of Colorado) — what normal KMT2A and menin actually do, which is the therapeutic-window question, The same pocket suppresses JUND: menin inhibition's unmeasured endocrine liability in infants
197. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23192350
     Silencing α1,3-fucosyltransferases in human leukocytes reveals a role for FUT9 enzyme during E-selectin-mediated cell adhesion.

     Buffone A, Mondal N, Gupta R, McHugh KP, Lau JT, Neelamegham S · J Biol Chem 2013
     used by FUT4 - the myeloid alpha-1,3-fucosyltransferase, a hub gene of the KMT2A-rearranged expression module, and the gene HGNC once officially called CD15
198. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24183680
     Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas

     Bender S, Tang Y, Lindroth AM, et al. · Cancer Cell 2013
     used by GSE225028: SUV39H1 and H3K9me3 CUT&RUN in SU-DIPG13 and SU-DIPG36 - the only published human SUV39H1 occupancy map deposited as a readable hg38 bigWig, and the enzyme and its own mark were profiled in the same cells
199. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23260488
     H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation.

     Hu G, Cui K, Northrup D, Liu C, Wang C, Tang Q, et al. · Cell Stem Cell 2013
     used by H2AZ1 - the one histone variant with a direct KMT2A-fusion paper: MLL-AF10 and MLL-ENL recruit Tip60 to Hoxa9 to acetylate H2A.Z
200. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23475131
     MBTD1 is associated with Pr-Set7 to stabilize H4K20me1 in mouse oocyte meiotic maturation

     Luo YB, Ma JY, Zhang QH, et al. · Cell Cycle 2013
     used by H4K20me1 - the transcription- and replication-linked H4 state, whose gene-body level tracks Pol II; it HAS been profiled genome-wide in human haematopoietic stem cells twice, and a query scoped to 'leukemia' cannot see either dataset, MBTD1 - the H4K20me1/me2 reader inside NuA4/TIP60, the quiescence brake on adult haematopoietic stem cells, and the 3' partner of ZMYND11::MBTD1 whose methyl-lysine cage the fusion carries and does not use
201. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23696748
     HDAC7 is a repressor of myeloid genes whose downregulation is required for transdifferentiation of pre-B cells into macrophages.

     Barneda-Zahonero B, Román-González L, Collazo O, Rafati H, Islam AB, Bussmann LH, di Tullio A, De Andres L, Graf T, López-Bigas N, Mahmoudi T, Parra M · PLoS Genet 2013
     used by HDAC7 - the eraser the index fusion silences, where the proposed therapy is to INDUCE the HDAC, and two 2024-2025 papers point in opposite directions
202. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23472968
     HMGA1 overexpression correlates with relapse in childhood B-lineage acute lymphoblastic leukemia.

     Roy S, Di Cello F, et al. · Leukemia & Lymphoma 2013
     used by HMGA1 (P17096) - an AT-hook architectural protein that antagonises histone H1 at scaffold-attachment regions, with a childhood B-ALL relapse correlation that is title-only evidence
203. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 24319237
     Treatment of infant leukemias: challenge and promise

     Brown P · Hematology Am Soc Hematol Educ Program 2013
     used by How many children this affects, How many infants worldwide, not just in the United States, Hypothesis: the KMT2A break can be prevented rather than the fusion treated - stated so it can be killed, and it probably should be, Is the drug target always in the retained half? An audit of the project's own framing, KMT2A / MLL1 — the gene that breaks, KMT2A-rearranged acute leukemia across all ages: infants are 4% of it, The national scale: about 24 infants a year in England and Wales, about 12 in Australia, What 160 infants a year actually permits: the sample-size arithmetic, Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata
204. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23649634
     HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells

     Zhao H, Zhang X, Frazão JB, Condino-Neto A, Newburger PE · Journal of Cellular Biochemistry 114(10):2375-83 2013
     used by HOXA-AS2 and HOXA-AS3 — mid-cluster antisense transcripts with essentially no KMT2A-r evidence
205. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24057258
     MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene

     Dou L, Li J, Zheng D, Li Y, Gao X, Xu C, Gao L, Wang L, et al. · Molecular Biology Reports 40:6811-6819 2013
     used by HOXA7 - the one HOXA paralogue besides HOXA9 with a published loss-of-function requirement for MLL-fusion transformation, and the requirement was shown in vitro only
206. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23865046
     Interference with RUNX1/ETO leukemogenic function by cell-penetrating peptides targeting the NHR2 oligomerization domain

     Bartel Y, Grez M, Wichmann C · BioMed Research International 2013
     used by Hypothesis — forced-oligomerisation interfaces are the mutation-resistant drug targets the fusion field has been ignoring, Mechanism class 2 — transcription-factor corruption (RUNX1::RUNX1T1, PML::RARA, ETV6::RUNX1, CBFB::MYH11) — a balance, not a pure dominant negative
207. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23744037
     An MLL-dependent network sustains hematopoiesis.

     Artinger EL, Mishra BP, Zaffuto KM, Li BE, Chung EKY, Moore AW, Chen Y, Cheng C, Ernst P · Proc Natl Acad Sci U S A 2013
     used by Hypothesis: the menin-MLL complex writes the same mark onto two address lists with opposite cell-state outputs, and which one a tissue reads decides whether blocking menin is a therapy or a lesion, KMT2A / MLL1 — the gene that breaks, Patricia Ernst (University of Colorado) — what normal KMT2A and menin actually do, which is the therapeutic-window question, Quiescence in the blood stem cell is actively held there by MLL1 - and losing MLL1 pushes the stem cell INTO cycle while pulling the progenitor OUT of it, The cell types that need MLL1 are the uncommitted ones - dependence ends exactly where lineage commitment begins
208. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24267891
     ATR prohibits replication catastrophe by preventing global exhaustion of RPA.

     Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH, Povlsen LK, Bekker-Jensen S, Mailand N, Bartek J, Lukas J · Cell 155(5):1088-103 2013
     used by If RPA loading at the KMT2A breakpoint cluster region is the licensing step for the etoposide-induced translocation, then the nuclear RPA reserve is a modifier of therapy-related KMT2A-rearranged leukaemia risk - and an ATR inhibitor, which kills by exhausting RPA, would raise that risk rather than lower it, Repeat the one published RPA-at-the-KMT2A-breakpoint experiment in a haematopoietic cell, with an RPA-dose arm - the protocol is fully specified in a 2010 paper whose every arm used fibroblasts and a CML line, and whose primer sets, dose and controls are all published, RPA-coated single-stranded DNA is the structure that licenses ATR: ATRIP reads it, ATR is brought to the lesion, and CHK1 is activated - which is how this corpus's ATR and CHEK1 entries connect to the clamp that had no entry until now, The replication protein A heterotrimer (RPA1/RPA2/RPA3) - the ssDNA clamp that every resection and replication-stress claim in this corpus silently depends on, and which had no entry until cycle 160
209. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23640942
     Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains.

     Wächter K, Köhn M, Stöhr N, Hüttelmaier S · Biol Chem 2013
     used by IGF2BP2 — the paralogue co-over-expressed with IGF2BP3 in MLL/AF4 B-ALL, and the one with an inhibitor in another leukaemia
210. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23508102
     Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes.

     van Nuland R, Smits AH, Pallaki P, Jansen PW, Vermeulen M, Timmers HT · Mol Cell Biol 2013
     used by In a cell with no fusion, a menin inhibitor is substantially a KMT2B drug, KMT2B (MLL2/MLL4) - the other protein menin binds, and the one this graph never wrote, KMT2C (MLL3) - the fetal brake on MLL-rearranged leukaemia, and a 7q tumour suppressor chemotherapy selects against, KMT2D (MLL2/MLL4) - the gene named in this graph's menin-resistance entry, written here for the first time, Menin holds KMT2A and KMT2B, and the graph has been written as if it held one, MLL2 and MLL4 each name two different genes, and the ambiguity is in the papers, not in the databases, PAXIP1 (PTIP) - the subunit that tells an MLL3/4 complex apart from a menin complex, and the only one with a leukaemic-niche phenotype, Tag endogenous KMT2B in an index-fusion line and measure what revumenib does to it - the experiment the reagents have blocked, The KMT2-family beat's own ledger: every query run, every gene dropped, every paper read and not used, When a family shares a complex, the result is family-selective, not member-selective - the protein version of this graph's inhibitor-class rule
211. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24244196
     Crosstalk between NSL histone acetyltransferase and MLL/SET complexes: NSL complex functions in promoting histone H3K4 di-methylation activity by MLL/SET complexes

     Zhao X, Su J, Wang F, Liu D, Ding J, Yang Y, Conaway JW, Conaway RC, Cao L, Wu D, Wu M, Cai Y, Jin J · PLoS Genetics 9(11):e1003940 2013
     used by KANSL1 - the NSL scaffold, and the protein through which WDR5 binding to NSL and to MLL/COMPASS is mutually exclusive, NSL complex - the MOF assembly that five NUP98 fusions bind alongside MLL1, and that competes with MLL/COMPASS for WDR5, WDR5 is partitioned, not shared: NSL and SET1/MLL complexes compete for one pool, so perturbing NSL changes how much WDR5 reaches the wild-type KMT2A complex the fusion depends on
212. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23403319
     Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

     Driessen EMC, van Roon EHJ, Spijkers-Hagelstein JAP, Schneider P, de Lorenzo P, Valsecchi MG, Pieters R, Stam RW · Haematologica 98(6):937-44 2013
     used by Kinase/PI3K/RAS pathway activation — the only common co-lesion class in KMT2A-r leukemia, and it is mostly subclonal, KRAS - the commonest co-mutation in a disease that has almost none, and it is usually in a minority of the cells, KRAS as a co-mutation in KMT2A-r leukemia — the single most frequently co-mutated gene, and it still cannot start the disease, NRAS - the other RAS, the one whose 0.3% clone came back, and a UniProt record that lists HRAS1 as its own synonym, NRAS as a co-mutation in KMT2A-r leukemia — the one co-lesion that is specifically enriched in t(4;11), The RAS-mutant subclone is where the leukaemia goes, not what it is - a dissemination modifier that a marrow aspirate systematically under-counts
213. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23100278
     Genomic breakpoints and clinical features of MLL-TET1 rearrangement in acute leukemias.

     Lee SG, Cho SY, Kim MJ, Oh SH, Cho EH, Lee S · Haematologica 2013
     used by KMT2A::TET1 (MLL-LCX), t(10;11)(q22;q23) — the fusion that throws away a second CXXC domain, TET1 (LCX / CXXC6) - a CXXC reader that is also a KMT2A fusion partner, and whose leukaemic fusion throws its own CXXC domain away
214. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23698361
     Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling.

     Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H · Nature 2013
     used by KRAS - the commonest co-mutation in a disease that has almost none, and it is usually in a minority of the cells
215. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23206227
     Lineage switch from pro-B acute lymphoid leukemia to acute myeloid leukemia in a case with t(12;17)(p13;q11)/TAF15-ZNF384 rearrangement.

     Grammatico S, Vitale A, La Starza R, Gorello P, Angelosanto N, Negulici AD, De Propris MS, Nanni M, Meloni G, Mecucci C, Foa R · Leuk Lymphoma 2013
     used by Lineage switch to myeloid leukaemia under CD19-directed therapy in ZNF384-rearranged ALL - and in the one cohort that caught both families, the ZNF384 switch looked mutationally NOTHING like the KMT2A ones
216. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24186981
     Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements

     Alfieri C, Gambetta MC, Matos R, et al. · Genes & Development 2013
     used by MBTD1 - the H4K20me1/me2 reader inside NuA4/TIP60, the quiescence brake on adult haematopoietic stem cells, and the 3' partner of ZMYND11::MBTD1 whose methyl-lysine cage the fusion carries and does not use
217. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23979164
     Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells.

     Goyama S, Schibler J, Cunningham L, et al. · Journal of Clinical Investigation 2013
     used by Mechanism class 2 — transcription-factor corruption (RUNX1::RUNX1T1, PML::RARA, ETV6::RUNX1, CBFB::MYH11) — a balance, not a pure dominant negative, RUNX1::RUNX1T1 (AML1-ETO), t(8;21)(q22;q22)
218. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23235717
     Cell of origin determines clinically relevant subtypes of MLL-rearranged AML

     Krivtsov AV, Figueroa ME, Sinha AU, Stubbs MC, Feng Z, Valk PJ, Delwel R, Döhner K, et al. · Leukemia 27:852-860 2013
     used by MECOM (EVI1) - a cell-of-origin memory that MLL-AF9 maintains but cannot install, present in about 43% of MLL-rearranged AML and marking the chemoresistant half
219. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 23523389
     Acute lymphoblastic leukaemia

     Inaba H, Greaves M, Mullighan CG · Lancet 2013
     used by Mel Greaves (Centre for Evolution and Cancer, ICR London) — natural history, in-utero origin and the prevention question
220. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23867312
     Hepatic menin recruits SIRT1 to control liver steatosis through histone deacetylation.

     Cao Y, et al. · J Hepatol 2013
     used by Menin is a corepressor of the LXR sterol sensors - one paper supplies three of this graph's twelve missing partners, and the function has never been written down here
221. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23798388
     miR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia-rearranged leukemia

     Chen P, Price C, Li Z, Li Y, Cao D, Wiley A, He C, Gurbuxani S, Kunjamma RB, Huang H, Jiang X, Arnovitz S, Xu M, Hong GM, Elkahloun AG, Neilly MB, Wunderlich M, Larson RA, Le Beau MM, Mulloy JC, Liu PP, Rowley JD, Chen J · Proceedings of the National Academy of Sciences USA 110(28):11511-6 2013
     used by miR-9 — the most MLL-specific microRNA in AML, encoded at three separate loci nobody has disambiguated
222. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23874665
     Msl2 is a novel component of the vertebrate DNA damage response.

     Lai Z, et al. · PLoS One 2013;8:e68549 2013
     used by MSL2 — the second H2B ubiquitin ligase, sitting inside the MOF complex the KMT2A fragment contacts
223. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23791785
     Class I HDACs share a common mechanism of regulation by inositol phosphates.

     Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JWR · Molecular Cell 2013
     used by MTA2 / MTA1L1 (O94776) - the NuRD scaffold that clamps HDAC1, recruited in T lymphocytes by BCL11B, and absent together with MTA1 and MTA3 from every column of the pan-MLL-fusion interactome, The NuRD complex - two separable modules, three paralogue choices that change what it does, and a graph that carried its ATPase and its shared core but never the scaffolds that make it NuRD
224. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24010737
     MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.

     Zhou C, Ji J, Cai Q, Shi M, Chen X, Yu Y, Liu B, Zhu Z, Zhang J · Molecular Cancer 2013
     used by MTA2 / MTA1L1 (O94776) - the NuRD scaffold that clamps HDAC1, recruited in T lymphocytes by BCL11B, and absent together with MTA1 and MTA3 from every column of the pan-MLL-fusion interactome
225. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24140114
     Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency.

     · Am J Hum Genet 2013
     used by NFKB2 (p100/p52) — menin binds the non-canonical subunit too, and activating that arm SUPPRESSES MLL-AF9 leukaemia
226. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23332751
     Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination.

     Nardini M, Gnesutta N, Donati G, Gatta R, Forni C, Fossati A, Vonrhein C, Moras D, Romier C, Bolognesi M, Mantovani R · Cell 2013
     used by NFYC / NF-YC - a histone-fold transcription factor whose partner subunit carries an H2B-like ubiquitination, and the most selective of the eleven TF baits that reached KMT2A
227. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23994619
     Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells.

     Largeot A, Paggetti J, Broseus J, Aucagne R, Lagrange B, Martin RZ, et al. · Biochim Biophys Acta 2013
     used by NUDT21 / CFIm25 (O43809) - the CFIm subunit that picks poly(A) sites, in the pan-MLL-fusion core, and a paraspeckle protein, WDR33 (Q9C0J8) - the subunit that reads AAUAAA, in the pan-MLL-fusion core, and the plant homolog of which physically links 3' processing to H3K4 demethylation
228. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23468646
     Dynamic association of NUP98 with the human genome

     Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer MW · PLoS Genet 2013
     used by NUP98 - the mobile nucleoporin that leaves the pore to put H3K4me3 on haematopoietic promoters, and the shared 5' donor of seven fusions in this graph
229. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePMID 23550210
     Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal

     Gao J, Aksoy BA, Dogrusoz U, et al. · Sci Signal 6:pl1 2013
     used by Only one public B-lineage cohort annotates the KMT2A fusion PARTNER per sample beside an expression matrix - every other large paediatric leukaemia resource records only 'MLL yes/no' or the 11q23 band
230. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24162813
     Differential regulation of myeloid leukemias by the bone marrow microenvironment

     Krause DS, Fulzele K, Catic A, Sun CC, Dombkowski D, Hurley MP, et al. · Nature Medicine 2013
     used by Osteoblast — the bone-building niche cell whose expansion suppresses CML and makes MLL-AF9 AML worse
231. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23670296
     Detection of PICALM-MLLT10 (CALM-AF10) and outcome in children with T-lineage acute lymphoblastic leukemia.

     Lo Nigro L, et al. · Leukemia 2013
     used by Outcome in PICALM::MLLT10: children with ALL do reasonably well, children with AML do badly, and transplant does not rescue them
232. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23264595
     PBX3 is an important cofactor of HOXA9 in leukemogenesis.

     Li Z, Zhang Z, Li Y, et al., Chen J · Blood 2013
     used by PBX2 - an AFF4 co-purifying protein in two rounds of one AP-MS atlas, and the PBX paralogue the leukaemia literature explicitly excluded, PBX3 - the TALE cofactor the field says is non-redundant, and the experiment that says HOXA9 is the redundant one, The HOX-PBX interface, and its one peptide: HXR9/HTL001 has been tried in eight tumour types and in KMT2A-rearranged leukaemia exactly once, The PBX requirement in KMT2A-rearranged leukaemia is a family property, and every experiment that shaped this graph's view of it removed one paralogue at a time
233. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23228662
     Tudor domains of the PRC2 components PHF1 and PHF19 selectively bind to histone H3K36me3

     Qin S, Guo Y, Xu C, Bian C, et al. · Biochem Biophys Res Commun 2013
     used by PHF1 (PCL1) - the PRC2 accessory subunit whose Tudor domain reads H3K36me3, and the 3' acceptor shared by three different NuA4-donor fusions in two different tumour types
234. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23512250
     Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations.

     Xu H, Yang W, Perez-Andreu V, et al. (27 authors; senior author Yang JJ) · J Natl Cancer Inst 2013
     used by PIP4K2A - the lipid kinase at a genome-wide childhood-ALL susceptibility locus, whose product is the ligand a PHD finger reads
235. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 23734343
     Differential Roles of PML Isoforms

     Nisole S, Maroui MA, Mascle XH, Aubry M, Chelbi-Alix MK · Frontiers in Oncology 3:125 2013
     used by PML K160 SUMOylation - the retained-portion PTM that became an approved therapy, and the benchmark every other retained site should be measured against
236. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23841729
     Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

     Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U · N Engl J Med 2013
     used by PML::RARA, t(15;17)(q24;q21), Why PML::RARA became curable — and what KMT2A::AFF1 does not share with it
237. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23623499
     MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells

     Maethner E, Garcia-Cuellar MP, Breitinger C, Takacova S, Divoky V, Hess JL, Slany RK · Cell Reports 2013
     used by Polycomb bodies — indirect evidence via CBX8, undercut by the finding that CBX8-PRC1 condensates are dissolved rather than built by the rest of PRC1, Polycomb in KMT2A-r leukemia — core PRC2 required, EZH2 and BMI1 dispensable, and CBX8 acting outside its repressive role, The lost SET domain, and the verdict: the fusion is a gain-of-function neomorph, not a KMT2A loss-of-function
238. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23222848
     Rare allelic forms of PRDM9 associated with childhood leukemogenesis

     Hussin J, Sinnett D, Casals F, et al. (Awadalla P, senior author) · Genome Research 23(3):419-30 2013
     used by PRDM9 - a germline risk mechanism for childhood ALL that does not reach KMT2A
239. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 23374339
     Mechanisms of programmed DNA lesions and genomic instability in the immune system

     Alt FW, Zhang Y, Meng FL, Guo C, Schwer B · Cell 2013
     used by RAG off-target activity: the dominant mutator in ETV6::RUNX1 ALL, and probably not the cause of KMT2A fusions
240. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24100041
     Identification of Wilms' tumor 1-associating protein complex and its role in alternative splicing and the cell cycle.

     Horiuchi K, Kawamura T, Iwanari H, Ohashi R et al. · J Biol Chem 2013
     used by RBM15 — m6A adaptor, AMKL fusion partner, and a named hit in the only KMT2A-biased RNA-protein CRISPR screen
241. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24089019
     A chimeric RNA characteristic of rhabdomyosarcoma in normal myogenesis process

     Yuan H, Qin F, Movassagh M, Park H, Golden W, Xie Z, Zhang P, Sklar J, Li H · Cancer Discovery 2013
     used by RNA-targeting the fusion transcript: verdict THE LEAST HOPELESS of the three fusion-level routes, blocked by delivery rather than by biology, Trans-splicing: healthy human cells make cancer-associated fusion transcripts without any chromosome rearrangement
242. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23628958
     The MLL recombinome of acute leukemias in 2013

     Meyer C, ... Marschalek R · Leukemia 2013
     used by Rolf Marschalek & Claus Meyer (DCAL, Goethe-University Frankfurt) — the world's KMT2A breakpoint dataset
243. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 23879542
     Contributions of the histone arginine methyltransferase PRMT6 to the epigenetic function of RUNX1.

     · Crit Rev Eukaryot Gene Expr 2013
     used by RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11)
244. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23563689
     Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment

     Will B, Vogler TO, Bartholdy B, Garrett-Bakelman F, Mayer J, Barreyro L, et al. · Nat Immunol 2013
     used by SATB1 - a nuclear-matrix and PML-body genome organiser with its own matrix-targeting sequence, the clearest subnuclear-localization entry in this beat, and a T-lineage factor that B cells do not need
245. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23894581
     A dual role for SAGA-associated factor 29 (SGF29) in ER stress survival by coordination of both histone H3 acetylation and histone H3 lysine-4 trimethylation.

     Schram AW, Baas R, Jansen PW, Riss A et al. · PLoS One 2013
     used by SGF29 — a SAGA reader with a Tudor pocket, intermediate essentiality, and the best unexploited profile in this beat
246. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23540691
     Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma.

     Kadoch C, Crabtree GR · Cell 2013
     used by SMARCB1 (BAF47/INI1/SNF5) - zero entries, zero mentions and, on the evidence, correctly so: it is lost in primary AML rather than required, SS18 - a SWI/SNF subunit that is itself a fusion partner in another cancer, and a lineage-independent dependency in KMT2A-rearranged lines, Two published ways a fusion oncoprotein engages BAF - be a subunit, or recruit it with a disordered domain - and KMT2A has never been tested for either
247. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23823658
     Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011

     Olsson L, Castor A, Behrendtz M, Biloglav A, Forestier E, Paulsson K, Johansson B · Leukemia 28:302-10 2013
     used by SPRED1 - the RAS/MAPK brake whose deletion marks relapse in paediatric B-ALL, third-widest margin in the Q152 AFF1-only core
248. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23695662
     Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model.

     Liu B, Wang Z, Zhang L, Ghosh S, et al. · Nature Communications 2013
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
249. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23416387
     Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases.

     Cherblanc FL, Chapman KL, Brown R, Fuchter MJ · Nature Chemical Biology 2013
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
250. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24253444
     Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal.

     Postma AV, Alders M, Sylva M, et al. · J Med Genet 2013
     used by TBXT / brachyury - the notochord master regulator, and one of only two of 102 transcription-factor baits whose neighbourhood contained DOT1L
251. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     PDB entries 2MH0 (Solution NMR structure of the p300 Taz2:ETAD1 complex), 3U5V (Max-E47), 2QL2 (E47/NeuroD1 bHLH on DNA) and 6MGN (Id1-E47)

     RCSB Protein Data Bank · RCSB PDB 2013
     used by TCF3::PBX1 (E2A-PBX1), t(1;19)(q23;p13.3)
252. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23505375
     TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo

     Gomez-Herreros F, Romero-Granados R, Zeng Z, et al. · PLoS genetics 2013
     used by TDP2 unglues trapped topoisomerase II from the KMT2A locus - it suppresses translocations overall and manufactures one rare junction class
253. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23818607
     TET1 plays an essential oncogenic role in MLL-rearranged leukemia.

     Huang H, Jiang X, et al. · Proc Natl Acad Sci U S A 2013
     used by TET1 (LCX / CXXC6) - a CXXC reader that is also a KMT2A fusion partner, and whose leukaemic fusion throws its own CXXC domain away
254. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 24323992
     First description of the t(10;11)(q22;q23)/MLL-TET1 translocation in a T-cell lymphoblastic lymphoma, with subsequent lineage switch to acute myelomonocytic myeloid leukemia.

     Ittel A, Jeandidier E, et al. · Haematologica 2013
     used by TET1 (LCX / CXXC6) - a CXXC reader that is also a KMT2A fusion partner, and whose leukaemic fusion throws its own CXXC domain away
255. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 4IMY: The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat

     Schulze-Gahmen U, Upton H, Birnberg A, et al. · RCSB Protein Data Bank 2013
     used by The AFF-family N-terminus on cyclin T1: Kd 10 nM, a 2.94 A crystal, and every number in it measured on AFF4 rather than on AFF1
256. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24102134
     Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP.

     Liu F; Barsyte-Lovejoy D; Li F; Xiong Y; Korboukh V; Huang XP; Allali-Hassani A; Janzen WP; Roth BL; Frye SV; et al. · J Med Chem 2013
     used by The H3K9me1/2-CTCF brake: a KDM3B-G9a balance keeps the KMT2A breakpoint cluster region methyl-poor and CTCF-bound, and losing either end makes the locus amplify and rearrange - in epithelium, in primary cord-blood progenitors and in mice, UNC0642 - the G9a/GLP chemical probe that abolished doxorubicin-induced Kmt2a copy gain in mice, and the one intervention in this beat that has been given to an animal
257. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 23697932
     ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection.

     Long HK, Blackledge NP, et al. · Biochem Soc Trans 2013
     used by The human CXXC/CpG-reading family is exactly twelve proteins, and TET2 is not one of them
258. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23651431
     Allosteric communication in the KIX domain proceeds through dynamic repacking of the hydrophobic core.

     Bruschweiler S, Konrat R, Tollinger M · ACS Chem Biol 2013
     used by The KMT2A transactivation domain on the CBP KIX domain: a cooperative allosteric site at 2842-2858, solved three times, and thrown away by every breakpoint
259. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 2LXS: Allosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core

     Bruschweiler S, Konrat R, Tollinger M · RCSB Protein Data Bank 2013
     used by The KMT2A transactivation domain on the CBP KIX domain: a cooperative allosteric site at 2842-2858, solved three times, and thrown away by every breakpoint
260. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22921182
     Absence of global hypomethylation in promoter hypermethylated Mixed Lineage Leukaemia-rearranged infant acute lymphoblastic leukaemia

     Stumpel DJPM, Schneider P, van Roon EHJ, Pieters R, Stam RW · European Journal of Cancer 49(1):175-84 2013
     used by The KMT2A-r DNA methylation signature — focal hypermethylation, no global hypomethylation, and a hypomethylating agent that did not help
261. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23318960
     Impairing MLL-fusion gene-mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75).

     Méreau H, De Rijck J, et al. · Leukemia 2013
     used by The LEDGF hole, measured: every published LEDGF-removal experiment removes it BEFORE or AT transformation, and none treats an established leukaemia in an animal
262. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 23893660
     The silent mutational landscape of infant MLL-AF4 pro-B acute lymphoblastic leukemia

     Dobbins SE, Sherborne AL, Ma YP, Bardini M, Biondi A, Cazzaniga G, Lloyd A, Chubb D, Greaves MF, Houlston RS · Genes, Chromosomes & Cancer 52(10):954-60 2013
     used by The near-silent genome of infant KMT2A-r ALL — 1.3 non-silent mutations, and why that is bad news as well as good, The quiet genome, audited - the famous 1.3 mutations is a count of point mutations in the dominant clone, and all three of those words do work
263. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23453805
     ASH2L regulates ubiquitylation signaling to MLL: trans-regulation of H3 K4 methylation in higher eukaryotes.

     Wu L, Lee SY, Zhou B, Nguyen UT, Muir TW, Tan S, Dou Y · Mol Cell 2013
     used by The other arm of the crosstalk: H2Bub licenses H3K4 methylation through ASH2L and relieves a built-in COMPASS autoinhibition — and MLL3 does not respond at all
264. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23479570
     FLT3 activation cooperates with MLL-AF4 fusion protein to abrogate the hematopoietic specification of human ESCs

     Bueno C, Ayllón V, Montes R, et al. · Blood 2013
     used by The pluripotent stem-cell route has failed from both ends, and the failures are informative
265. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23902761
     A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks.

     Ismail IH, McDonald D, Strickfaden H, Xu Z, Hendzel MJ · J Biol Chem 2013
     used by There is no selective PRC1 catalytic inhibitor - the entire chemistry is one 2013 tool compound and its analogues, and it hits both paralogues by design
266. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23828889
     Real-time dynamics of RNA polymerase II clustering in live human cells

     Cisse II, Izeddin I, Causse SZ, Boudarene L, Senecal A, Muresan L, Dugast-Darzacq C, Hajj B, Dahan M, Darzacq X · Science 2013
     used by Transcription factories and Pol II clusters - no KMT2A::AFF1 imaging, condensate evidence for SEC and MLL-ENL, and 3D-FISH that actively contradicts the factory story for t(4;11)
267. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23362228
     Histone acetyltransferase cofactor Trrap maintains self-renewal and restricts differentiation of embryonic stem cells.

     Sawan C, Hernandez-Vargas H, Murr R, Lopez F, Vaissière T, Ghantous AY, Cuenin C, Imbert J, Wang ZQ, Ren B, Herceg Z · Stem Cells 2013
     used by TRRAP — a 3,859-residue DotCom subunit that every cell needs and no KMT2A cell needs more
268. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24130053
     Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells

     · Molecular Cancer Therapeutics 2013
     used by USP1: an inhibitor, activity in B-ALL, and zero papers in the disease we care about
269. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 24190124
     Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude Lifetime Cohort Study

     Krull KR, Brinkman TM, Li C, Armstrong GT, Ness KK, Srivastava DK, Gurney JG, Kimberg C, Krasin MJ, Pui CH, Robison LL, Hudson MM · Journal of Clinical Oncology 2013
     used by What the treated brain looks like later: neurocognitive late effects after CNS-directed therapy in infancy
270. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23737213
     Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.

     Antonescu CR, Le Loarer F, Mosquera JM, et al. · Genes Chromosomes Cancer 2013
     used by YAP1 (P46937) - the Hippo pathway's transcriptional co-activator, and a KMT2A fusion partner from a completely different functional class
271. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 24101467
     Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1 transcription.

     Xu B, Li SH, Zheng R, et al. · Proc Natl Acad Sci U S A 2013
     used by YAP1 (P46937) - the Hippo pathway's transcriptional co-activator, and a KMT2A fusion partner from a completely different functional class
272. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 24270879
     The human cap-binding complex is functionally connected to the nuclear RNA exosome.

     Andersen PR, Domanski M, Kristiansen MS, Storvall H, Ntini E, et al. · Nat Struct Mol Biol 2013
     used by ZC3H18 (Q86VM9) - the CBC-to-exosome bridge in the pan-MLL-fusion core, and the ONLY member of this tranche whose own complex came with it
273. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22412018
     A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells.

     Roux KJ, et al. · J Cell Biol 2012
     used by A BioID hit is a neighbour, not a complex member - and the two methods are known to disagree
274. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22327296
     The same pocket in menin binds both MLL and JUND but has opposite effects on transcription.

     Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, et al. · Nature 2012
     used by A residue axis for menin, derived from coordinates: three spatial lobes, not four named ones, and the sharpest seam in the protein runs through the drug pocket, Agency law — actual authority, apparent authority, and what revocation cannot undo, Analysis (runnable): can a menin ligand tell KMT2A from JUND? A structural and co-folding selectivity profile of the whole inhibitor class, CK2 phosphorylation of KMT2A S136/S142 tunes the LEDGF grip - a second, non-menin, phospho-gated handle on the fragment every fusion keeps, Does revumenib displace JunD, and at what concentration relative to KMT2A? (The yes/no half is already answered), Fiduciary conflict of interest — law does not remove a conflicted agent, it separates the mandates, How menin silences JunD: pocket binding plus uncoupling from MAP kinase signalling, Hypothesis: menin inhibitors differ in how much JUND they liberate, and the least JUND-liberating compound will be the most durable, Hypothesis: the PTH rise on menin inhibitors is on-target and exposure-dependent, not renal, JUND liberation — the drug's mechanism of action and one of its mechanisms of resistance are the same event, KMT2B, AFF2, AFF3, AFF4 and ENL carry most of the contact residues of the two interfaces the fusion keeps (menin-KMT2A and AF9-AFF1), so a substitute is structurally possible and selectivity cannot be read from either surface; at the menin side KMT2B differs at W7, LEDGF IBD to KMT2A: TWO motifs, not one - IBM1 at 124-133 and IBM2 at 147-152, and the Kd this graph recorded as missing is 14.7 uM, MBM2, the second menin-binding motif of KMT2A (residues 23-40): 26-fold weaker than MBM1, never separately co-crystallised, and the only part of the menin grip a drug is not aimed at, Measure the menin-KMT2B affinity nobody has measured, and the four clinical inhibitors' IC50 against it, Menin dependence of a non-elongation KMT2A fusion has never been demonstrated — the counted absence, and what the pivotal trial actually enrolled, Menin is the best-observed of the six core proteins and the only one whose interval separates from the rest - the interface the programme is built on is the one the record actually supports, Menin-JunD: the same pocket, the same drug, the opposite job, Phase-2 dossier: the menin MBM1 pocket - the only candidate here that is already de-risked, and therefore the only one whose gate is clinical, Releasing JunD does not merely de-repress it: JunD without menin becomes a growth promoter, The interactome instrument is migrated to IntAct REST: 277 partners, 118 written, 42.6% - the denominator grew by 60 and coverage fell 3.5 points, which is the instrument getting honest, The menin acidic shelf, Glu366-Asp370-Val371: the counter-charge that MBM2 binds, resolved in 3U88 after all - and the one patch where the drug pocket, the SvID and the gamma-H2A.X motif all touch, The menin small-molecule pocket as a coordinated surface: four clinical-stage compounds, 21-26 contact residues each, and bleximenib sitting on a different part of it from the other three, The menin–KMT2A grip (MBM1), the interface the drugs actually block, The phase-2 go/no-go register: the numbers we agree to before we look, The result that runs the wrong way: in Psip1-null cells Hoxa and Hoxd expression goes UP, because Psip1 also recruits Bmi1 and Ctbp1, The same pocket suppresses JUND: menin inhibition's unmeasured endocrine liability in infants, The SvID, menin 360-445: a truncation boundary the field reads as a domain, whose functional residues D418 and W436 are 10-20 A from every menin drug - but whose first ten residues ARE the drug pocket, Two thirds of the curated interactome of this project's six core proteins is spoke-expanded - and the pairs this graph chose to write are significantly better than the ones it did not, What a curated interaction row actually claims: spoke expansion, and the ladder from 'was in the same tube' to 'touches'
275. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22547686
     The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output.

     Luo Z, Lin C, Guest E, Garrett AS, Mohaghegh N, Swanson S, Marshall S, Florens L, Washburn MP, Shilatifard A · Molecular and Cellular Biology 2012
     used by AFF2 (FMR2) — the SEC-L2 scaffold, and the AFF-family member with no dependency anywhere, AFF3 (LAF4) — the AFF-family scaffold of SEC-L3, and a KMT2A fusion partner in its own right, Hypothesis: YEATS-pocket occupancy disables the reader module of all three SEC-family complexes in proportion to how much of the reader pool each holds — so the drug's footprint is set by an unmeasured partition, not by the fusion, Measure the one number the whole YEATS-selectivity argument turns on: what fraction of ENL and of AF9 is in SEC, in SEC-L2, in SEC-L3 and free — with an exchange control, because the question may not be well posed, Scored against the literature: the composition half of the YEATS-selectivity objection holds and the selectivity half is refuted — a scaffold-blind probe already has an in vivo window in the index fusion with no HSPC toxicity, SEC — the AFF1/AFF4-scaffolded super elongation complex, the particle KMT2A::AFF1 is a permanent subunit of, SEC-L2 — the AFF2-scaffolded super-elongation-like complex: P-TEFb plus ENL and AF9, and NO ELL, SEC-L2 and SEC-L3 contain ENL and AF9 exactly as SEC does, so AFF2 and AFF3 sit in complexes built around the same acyl-lysine readers as the index fusion's partner - and both entries carry no epigenetics annotation at all, SEC-L3 — the AFF3-scaffolded complex, and the only SEC-family member with a known physiological job: genomic imprinting and X inactivation, The SEC-family target sets, reconstructed as a full three-way Venn: 27.5% of the family's transcriptional output is invisible to AFF4 depletion — and the two 'distinct' sibling sets overlap 8-20x more than chance, The shared reader sits in a complex whose only well-defined normal job is parent-of-origin silencing — and the published safety package for YEATS inhibition is entirely haematopoietic, Two surfaces, two jobs: the AHD picks the scaffold and the YEATS pocket reads the histone — so a YEATS ligand cannot ask which of the three SEC-family complexes it is disabling
276. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23249737
     Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4.

     Dhar SS, Lee SH, Kan PY, Voigt P, et al. · Genes Dev 2012
     used by An assay that cannot separate me2a from me2s cannot test the arginine switch - the two states are isobaric and predict OPPOSITE things, so a non-discriminating readout returns no information rather than an imprecise answer, Arginine methylation gates KMT2-complex access to chromatin at two residues, in both directions, independently of the menin tether AND of the WIN motif - a parallel control point, not a rival to menin dependence, H4R3me2a - the activating arginine mark that a KMT2-family enzyme's OWN tandem PHD module reads, where the Kabuki-syndrome mutations sit, and which no KMT2A-fusion study has ever measured, H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system, Measure H3R2 and H4R3 methylation states at KMT2A-fusion targets by isomer-resolving mass spectrometry, and test the gate by writer perturbation read out on the enzyme's product - the experiment that has never been done in any fusion, PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check
277. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22341456
     Spatial organization of the mouse genome and its role in recurrent chromosomal translocations

     Zhang Y, McCord RP, Ho YJ, et al. · Cell 2012
     used by Analysis (runnable): do KMT2A partners rank by nuclear contact frequency in the same order as they rank in patients?, Experiment: measure KMT2A-AFF1 spatial proximity in the human fetal progenitor, in the cell and at the time the translocation actually happens, How a chromosome translocation actually forms: proximity + breakage + repair, Why KMT2A picks AFF1: spatial proximity, shared transcription hubs, and the unsettled proximity-versus-damage question
278. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22314321
     DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

     Hakim O, Resch W, Yamane A, et al. · Nature 2012
     used by Analysis (runnable): do KMT2A partners rank by nuclear contact frequency in the same order as they rank in patients?, Experiment: measure KMT2A-AFF1 spatial proximity in the human fetal progenitor, in the cell and at the time the translocation actually happens, Hypothesis: KMT2A and AFF1 break where they do because both breakpoint regions are CTCF/cohesin loop anchors sitting in the same nuclear hub
279. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22615413
     Model for MLL translocations in therapy-related leukemia involving topoisomerase IIbeta-mediated DNA strand breaks and gene proximity

     Cowell IG, Sondka Z, Smith K, et al. · Proceedings of the National Academy of Sciences of the United States of America 2012
     used by Analysis (runnable): do KMT2A partners rank by nuclear contact frequency in the same order as they rank in patients?, Experiment: degrade TOP2A and TOP2B separately in a fetal-like human progenitor and map DNA breaks at the KMT2A locus without a poison, Experiment: measure KMT2A-AFF1 spatial proximity in the human fetal progenitor, in the cell and at the time the translocation actually happens, Hypothesis: KMT2A and AFF1 break where they do because both breakpoint regions are CTCF/cohesin loop anchors sitting in the same nuclear hub, Hypothesis: what breaks KMT2A in a fetus is TOP2B doing its normal transcription-coupled job in a non-cycling progenitor, with no poison involved and repair capacity as the rate-limiting variable, The KMT2A breakpoint cluster region: an 8.3 kb stretch built to break, TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically, Topoisomerase II cleavage and TOP2 poisons as a source of KMT2A breaks, Why KMT2A picks AFF1: spatial proximity, shared transcription hubs, and the unsettled proximity-versus-damage question
280. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22124095
     Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes - a report from the Children's Oncology Group

     Blanco JG, Sun CL, Landier W, Chen L, Esparza-Duran D, Leisenring W, Mays A, Friedman DL, Ginsberg JP, Hudson MM, Neglia JP, Oeffinger KC, Ritchey AK, Villaluna D, Relling MV, Bhatia S · Journal of Clinical Oncology 2012
     used by Anthracycline cardiotoxicity: the heart an infant keeps for sixty years
281. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22355166
     Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles.

     Miyagawa R, Tano K, Mizuno R, Nakamura Y, Ijiri K, Rakwal R, et al. · RNA 2012
     used by AQR (Aquarius) - a spliceosomal RNA helicase whose loss impairs MLL-rearranged leukaemia stem cells
282. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22722839
     The mutational landscape of lethal castration-resistant prostate cancer.

     Grasso CS, et al. · Nature 2012
     used by AR / androgen receptor - the best-supported partner in the absence set by independent-publication count, and the reason a menin inhibitor is in prostate cancer trials
283. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22231400
     Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance.

     Migliori V, Müller J, Phalke S, Low D, et al. · Nat Struct Mol Biol 2012
     used by Arginine methylation gates KMT2-complex access to chromatin at two residues, in both directions, independently of the menin tether AND of the WIN motif - a parallel control point, not a rival to menin dependence, H3R2me2a - the asymmetric arginine mark two residues from H3K4 that LOCKS the WRAD module off the histone tail, and the first arginine mark node in this graph, H3R2me2s - the symmetric mark on the SAME residue as H3R2me2a, which permits rather than enhances WRAD access, and whose 'enhancing' half this graph inherited from the paper that was later revised, PRMT5 - the type II arginine methyltransferase this graph has reached for sixteen times, whose mark on H3R2 RECRUITS WDR5 to chromatin, PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check
284. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22516260
     DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo.

     Takacova S, Slany R, Bartkova J, Stranecky V, Dolezel P, Luzna P, et al. · Cancer Cell 2012
     used by ATR - the replication-stress kinase with the best preclinical case in this disease and the best published reason not to inhibit it, CHEK2 (CHK2) - named in every combination mechanism here and measured on its own in none of them
285. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22373577
     Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.

     Wakeman TP, et al. · EMBO J 2012
     used by BAG6 / BAT3 - a DOT1L partner that is about H3K79me2 itself, reciprocally co-immunoprecipitated, and not a spoke
286. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 22210327
     The corepressors BCOR and BCORL1: two novel players in acute myeloid leukemia

     Tiacci E, Grossmann V, Martelli MP, Kohlmann A, Haferlach T, Falini B · Haematologica 97(1):3-5 2012
     used by BCORL1 — the BCOR paralogue that is in the only crystal structure of the PRC1.1 core, and is the one PRC1.1 subunit nobody has tested in KMT2A-rearranged leukaemia
287. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 22510298
     Diagnosis and management of neonatal leukaemia.

     van der Linden MH, Creemers S, Pieters R · Semin Fetal Neonatal Med 2012
     used by Big liver, big spleen: the organomegaly numbers measured in infants, not pooled from children, Leukaemia diagnosed in the first month of life: a different presentation and a different prognosis, Rash: the one presenting feature that gets commoner the younger the baby is
288. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22689681
     RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes

     Greif PA, Konstandin NP, Metzeler KH, Herold T, Pasalic Z, Ksienzyk B, Dufour A, Schneider F, Schneider S, Kakadia PM, Braess J, Sauerland MC, Berdel WE, Buchner T, Woermann BJ, Hiddemann W, Spiekermann K, Bohlander SK · Haematologica 97:1909-15 2012
     used by BLNK (SLP-65) - the B-cell receptor adapter, in the Q152 AFF1-only core and a known lineage-infidelity marker in myeloid leukaemia
289. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22281595
     Endothelial and perivascular cells maintain haematopoietic stem cells

     Ding L, Saunders TL, Enikolopov G, Morrison SJ · Nature 2012
     used by Bone-marrow sinusoidal endothelial cell — the vessel wall that keeps stem cells alive, and posts vesicles that accelerate MLL-AF9 leukaemia, CAR cell (CXCL12-abundant reticular) / LEPR+ perivascular stromal cell — the cell that makes the signal holding blood stem cells in the marrow, Every niche-disrupting drug strips the patient's own stem cells of the same shelter — the bite-back that applies to the whole beat, KITLG (stem cell factor) - the niche ligand of KIT, zero mentions anywhere in this graph, and its own symbol collides with the SCF ubiquitin ligase this corpus talks about constantly, LEPR - the marker that defines the SCF-supplying perivascular niche cell, the receptor for an adipocyte signal that blunts cytarabine, and a gene_exact query that returns the wrong protein first, Nestin+ mesenchymal stem cell — the niche cell that MLL-AF9 leukaemia wakes up and then loses, Osteoblast — the bone-building niche cell whose expansion suppresses CML and makes MLL-AF9 AML worse, The bone-marrow niche — the address a blood stem cell lives at, which 26 entries in this graph invoke and none had defined, The perivascular and sinusoidal niche — where the functional evidence actually sits, and where the marrow is genuinely hypoxic
290. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22978415
     Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L.

     Basavapathruni A, Jin L, Daigle SR, Majer CR, et al. · Chem Biol Drug Des 2012
     used by Bounding an absence the graph already asserts: the H3K79me2 decay half-life, counted, dated and controlled - and why three of the six hits are about the drug's half-life
291. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22683204
     Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells.

     Ceccaldi R, Parmar K, Mouly E, Delord M, Kim JM, Regairaz M, Pla M, Vasquez N, Zhang QS, Pondarre C, Peffault de Latour R, Gluckman E, Cavazzana-Calvo M, Leblanc T, Larghero J, Grompe M, Socié G, D'Andrea AD, Soulier J · Cell Stem Cell 2012
     used by BRIP1 — downstream effector; rank 22 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all, FAAP100 — FA core complex; rank 36 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all, FANCD2 — the FA effector menin binds, and the weakest FA gene in this graph's own selectivity scan, FANCF — FA core complex; rank 11 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all, FANCG — FA core complex; rank 27 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all, FANCI — ID2 module; rank 15 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all, Replication stress and interstrand-crosslink repair as a cell state - an ATR dependency measured in mouse MLL-rearranged AML, and the same stress implicated in breaking the MLL locus in the first place
292. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21706055
     The clathrin-binding domain of CALM-AF10 alters the phenotype of myeloid neoplasms in mice.

     Stoddart A, et al. · Oncogene 2012
     used by CALM-AF10 is predominantly cytoplasmic in transfected non-haematopoietic cells - and NUCLEAR in leukaemia cells (title corrected 2026-09-21; the five systems are five instances of one design), Where the break falls, and the three incompatible numbering frames that make it easy to get wrong
293. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22863532
     Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during asymmetric satellite stem cell divisions.

     Kawabe Y, Wang YX, et al. · Cell Stem Cell 2012
     used by CARM1 / PRMT4 (Q86X55) - the H3R17me2a writer, and the enzyme whose product is read by the KMT2A C-terminus that every fusion deletes
294. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23153540
     An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia

     Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Dohner K, Dohner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR · Cancer Cell 2012
     used by CBFA2T3::GLIS2, inv(16)(p13.3q24.3), Ordering the fusions developmentally — which stage of blood formation each one hijacks, and at what age the child presents, RUNX1::RUNX1T1 (AML1-ETO), t(8;21)(q22;q22)
295. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 22340903
     Establishment and characterization of a new human acute myelomonocytic leukemia cell line JIH-3.

     Pan J, Xue Y, Chen S, Qiu H, Wu C, Jiang H, Wang Q, Zhang J, Bai S, Wu Y, Wang Y, Shen J · Leuk Res 2012
     used by CDK13 - rank 171 of 17,728, equally deep in both lineage halves, and essentially unstudied in leukaemia
296. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22681891
     The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.

     Karpiuk O, Najafova Z, Kramer F, et al. · Mol Cell 2012
     used by CDK9 - the kinase the whole SEC story runs through, which this graph held only as half of a two-protein summary entry, Nobody knows which way to push H2Bub in this disease, and the only available compound pushes it upward, RNF40 (BRE1B) — the obligate partner of RNF20, and the one of the pair with a documented link to differentiation and bivalency resolution
297. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22649058
     Heterochromatin protein 1 gamma and IκB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages.

     Thorne JL, Ouboussad L, Lefevre PF · Nucleic Acids Res 2012
     used by CHUK (IKK-alpha) — the only kinase that sits in BOTH NF-kB arms, which makes it the one subunit whose inhibition has an ambiguous sign in this disease
298. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22941246
     Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin

     Kohn LA, Hao QL, Sasidharan R, Parekh C, Ge S, Zhu Y, et al., Crooks GM · Nature Immunology 2012
     used by Common lymphoid progenitor (CLP) — the CD10-positive lymphoid route that infant KMT2A leukaemia appears NOT to take
299. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23142979
     Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX.

     Liu CP, Xiong C, Wang M, et al. · Nature Structural & Molecular Biology 2012
     used by DAXX and ATRX as drug targets: six ChEMBL rows and zero of them an affinity, against menin's 1,776 - but three crystal structures of the interface that would have to be blocked
300. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22282267
     Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia.

     Spijkers-Hagelstein JA, Schneider P, Hulleman E, de Boer J, Williams O, Pieters R, et al. · Leukemia 2012
     used by Dexamethasone - the steroid an infant is actually on for most of the protocol, and the one with a high-certainty neurodevelopmental signal in babies, Prednisolone - the active steroid, the drug every resistance experiment in this disease actually used, and the one given into the spinal fluid
301. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22773103
     LEDGF (p75) promotes DNA-end resection and homologous recombination.

     Daugaard M, et al. · Nat Struct Mol Biol 2012
     used by Does a menin inhibitor break homologous recombination? Test the menin - SETD2 - LEDGF - CtIP chain in a blast, before the next genotoxic combination is designed, RBBP8 / CtIP - the only unwritten core-complex partner with a DIRECT-interaction record, and the graph already held its mechanism without holding the protein, The bite-back surface: LEDGF tethers CtIP to active chromatin and is required for DNA-end resection and homologous recombination
302. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3U86: Crystal structure of human menin in complex with JunD

     Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X, Lei M · RCSB Protein Data Bank 2012
     used by Does revumenib displace JunD, and at what concentration relative to KMT2A? (The yes/no half is already answered), JUND - the AP-1 subunit menin holds down, and the one a menin inhibitor lets go, Menin-JunD: the same pocket, the same drug, the opposite job
303. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23129768
     A subset of mixed lineage leukemia proteins has plant homeodomain (PHD)-mediated E3 ligase activity

     Wang J, Muntean AG, Wu L, Hess JL · Journal of Biological Chemistry 287(52):43410-43416 2012
     used by Does the fusion 'lose restraint'? The pattern of KMT2A-side loss, and why the tidy reading does not survive contact with the ledger, Experiment: put four residues back - the minimal add-back control the PHD3 result has never had, Hypothesis: what the KMT2A half loses is control of its own abundance, not control of its activity, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: PHD2 (aa 1479-1533), an E3 ubiquitin ligase that limits KMT2A's own activity
304. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22237106
     The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

     Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, et al., Mullighan CG · Nature 2012
     used by Early T-cell precursor (ETP) — the thymocyte that has not yet given up being myeloid, and where KMT2A-rearranged T-ALL sits
305. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22396593
     Polycomb repressive complex 2 is required for MLL-AF9 leukemia.

     Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L, et al. · Proc Natl Acad Sci U S A 2012
     used by EED - the PRC2 subunit this disease actually needs, with drugs in the clinic and zero leukaemia studies, EZH1 - the paralogue that makes the approved EZH2 drug the wrong drug for this disease, EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off, Point the EED inhibitor at the index fusion - a clinical-stage drug, a subunit with no paralogue, and zero leukaemia experiments, Polycomb in KMT2A-r leukemia — core PRC2 required, EZH2 and BMI1 dispensable, and CBX8 acting outside its repressive role, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, Tazemetostat - an approved EZH2 inhibitor, and the drug this disease's own biology predicts will not work
306. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23273992
     The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation.

     Lin C, Garruss AS, Luo Z, Guo F, Shilatifard A · Cell 2012
     used by ELL3 — the third ELL paralogue, which marks enhancers and recruits SEC rather than sitting inside it
307. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22002106
     Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization.

     Ahmad Y, Boisvert FM, et al. · Mol Cell Proteomics 2012
     used by ELP3 - the catalytic subunit, the only Elongator protein with a real acetyltransferase domain, and the one whose loss in mouse blood causes marrow failure and then p53-mutant leukaemia
308. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22854966
     DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator.

     Close P, Gillard M, Ladang A et al · Journal of Biological Chemistry 2012
     used by ELP4 (PAXNEB) - a required subunit of Elongator, the one partner of the seven with a genuine histone-acetyltransferase connection, and the one whose fusion supplies only its last 43 residues, ELP5 (DERP6) - the bridge that joins ELP3 to ELP4, the most essential Elongator subunit in DepMap, and a gene whose cytoplasmic call rests on an overexpression experiment, ELP6 (TMEM103/C3orf75) - an Elongator subunit named after a membrane protein it is not, whose entire localisation record comes from a Drosophila paper its own symbol cannot retrieve
309. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22645656
     Drosophila poly suggests a novel role for the Elongator complex in insulin receptor-target of rapamycin signalling.

     Bolukbasi E, Vass S, et al. · Open Biol 2012
     used by ELP6 (TMEM103/C3orf75) - an Elongator subunit named after a membrane protein it is not, whose entire localisation record comes from a Drosophila paper its own symbol cannot retrieve
310. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23077088
     Abnormalities of the der(12)t(12;21) in ETV6-RUNX1 acute lymphoblastic leukemia

     Al-Shehhi H, Konn ZJ, Schwab CJ, Erhorn A, Barber KE, Wright SL, Gabriel AS, Harrison CJ, Moorman AV · Genes Chromosomes Cancer 2012
     used by ETV6::RUNX1 (TEL-AML1), t(12;21)(p13;q22)
311. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22275876
     Progressive polycomb assembly on H3K27me3 compartments generates polycomb bodies with developmentally regulated motion.

     Cheutin T, Cavalli G · PLoS Genet 2012
     used by EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off
312. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22653977
     FANCL ubiquitinates β-catenin and enhances its nuclear function.

     Dao KH, Rotelli MD, Petersen CL, Kaech S, Nelson WD, Yates JE, Hanlon Newell AE, Olson SB, Druker BJ, Bagby GC · Blood 2012
     used by FANCL — FA core complex; rank 26 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
313. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23107779
     Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia.

     Geng H, Brennan S, Milne TA, et al. · Cancer Discov 2012
     used by FLT3 / CD135 — the strongest non-tether co-dependency, and a target the field may have written off on a badly executed trial
314. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22072553
     Identification and characterization of Hoxa9 binding sites in hematopoietic cells.

     Huang Y, Sitwala K, Bronstein J, et al. · Blood 2012
     used by FLT3 / CD135 — the strongest non-tether co-dependency, and a target the field may have written off on a badly executed trial, MEIS1 — rate-limiting for MLL leukemia stem cells, a surviving co-dependency, and embryonic-lethal when removed
315. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22210879
     Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study

     Kang H, Wilson CS, Harvey RC, Chen IM, Murphy MH, Atlas SR, et al. · Blood 119(8):1872-81 2012
     used by FLT3 in KMT2A-r leukemia — near-universal overexpression, but activating mutation in only ~3% of infants, GSE68720 - 97 infant ALL patients from COG P9407 with the KMT2A partner named per sample (mll_par) and a GPL570 expression matrix, 74 partner-named KMT2A-r cases and 17 germline controls, In infant ALL, IRX1 transcript is enriched in KMT2A::AFF1 (21 of 48) and present but rare outside it (3 of 26) - so the occupancy zero outside AFF1 is not an expression zero, IRX1 status is set by the cell of origin, and the fusion partner predicts it only because different partners transform different cells - so the partner supplies no IRX1 address, IRX2 - the IRX-cluster neighbour that is this disease's own prognostic gene, activated only in KMT2A::AFF1, and never written here until now, Measure IRX1 transcript and KMT2A-N oncoprotein occupancy in the SAME KMT2A::EPS15 blast - the one cell where expression-without-occupancy is most likely and has never been paired, No KMT2A-rearranged haematopoietic cell line in CCLE expresses IRX1 - including all four KMT2A::AFF1 lines MV4-11, NALM-19, RS4;11 and SEM at 0.0000-0.0053 RPKM, PROM1/CD133 tracks the HOXA arm and ANTI-tracks the IRX1 arm in 48 KMT2A::AFF1 infant ALL cases - so the one surface target with a published human kill is depleted in the iALL-IRX1 subgroup, The HOXA/IRX1 mutual exclusivity is reproduced at the transcript level in 48 KMT2A::AFF1 infant ALL cases (Fisher two-sided p < 1e-6) and is ABSENT in KMT2A::MLLT1 and in KMT2A-germline controls, Three of seventeen KMT2A-GERMLINE infant ALL cases are IRX1-high, one at 10.37 - so a high IRX1 in an infant leukaemia is not by itself evidence of anything fusion-related, Two of three KMT2A::EPS15 infant ALL cases carry IRX1 at KMT2A::AFF1 magnitude, while the only KMT2A::EPS15 patient with occupancy data has no oncoprotein at IRX1 at all
316. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 22652693
     WRAD: enabler of the SET1-family of H3K4 methyltransferases.

     Ernst P, Vakoc CR · Brief Funct Genomics 2012
     used by Four ways a WDR5 result can be true and have nothing to do with KMT2A, The founding WRAD negative was never run on a fusion protein, WDR5: an established wild-type KMT2A contact, and no fusion contact ever measured
317. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22464800
     The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells.

     Harris WJ; Huang X; Lynch JT; Spencer GJ; Hitchin JR; Li Y; et al. · Cancer Cell 2012
     used by H3K4me2 - the LSD1 substrate, and the only histone mark ever compared head-to-head between two KMT2A fusion partners in human cells, KDM1A (LSD1) — acts at the loci the fusion binds, spares normal stem cells, and still has never been shown to touch the fusion protein
318. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22615488
     KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemia.

     Kim JY; Kim KB; Eom GH; Choe N; Kee HJ; Son HJ; Oh ST; Kim DW; Pak JH; Baek HJ; et al. · Mol Cell Biol 2012
     used by H3K9me2 - named sixty times in this graph with no entry of its own, the mark that defines the lamina-associated domains the fusion's targets sit beside, and the only H3K9 methylation state ever measured at a KMT2A fusion's own binding sites, KDM3B - the H3K9me1/2 demethylase that sits on the KMT2A breakpoint cluster region and keeps it from rearranging, and the only leukaemia gene in this graph whose direction of effect flips between the myeloid and the lymphoid literature
319. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22241471
     Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming omega-NG-monomethylated arginine residues.

     Zurita-Lopez CI, Sandberg T, Kelly R, Clarke SG · J Biol Chem 2012
     used by H3R2me2s - the symmetric mark on the SAME residue as H3R2me2a, which permits rather than enhances WRAD access, and whose 'enhancing' half this graph inherited from the paper that was later revised, H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system, PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check
320. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22689669
     The role of WDR5 in silencing human fetal globin gene expression.

     Xu Z, He Y, Ju J, Rank G, et al. · Haematologica 2012
     used by H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system
321. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22981233
     Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures

     Choi KD, Vodyanik MA, Togarrati PP, Suknuntha K, Kumar A, Samarjeet F, Probasco MD, Tian S, Stewart R, Thomson JA, Slukvin II · Cell Reports 2012
     used by Haemogenic endothelium — the vessel-wall cell that gives birth to blood
322. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22212479
     A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

     Bueno C, Montes R, Melen GJ, Ramos-Mejia V, Real PJ, Ayllón V, Sanchez L, Ligero G, Gutierrez-Aranda I, Fernández AF, Fraga MF, Moreno-Gimeno I, Burks D, Plaza-Calonge MdelC, Rodríguez-Manzaneque JC, Menendez P · Cell Research 2012
     used by Haemogenic endothelium — the vessel-wall cell that gives birth to blood, Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one, The pluripotent stem-cell route has failed from both ends, and the failures are informative
323. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23000143
     A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability.

     Huang L, Jolly LA, Willis-Owen S, Gardner A, Kumar R, Douglas E, Shoubridge C, Wieczorek D, Tzschach A, Cohen M, Hackett A, Field M, Froyen G, Hu H, Haas SA, Ropers HH, Kalscheuer VM, Corbett MA, Gecz J · Am J Hum Genet 2012
     used by HCFC1 (HCF-1) — a founding member of the wild-type KMT2A complex that the fusion cannot bind
324. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22952229
     Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein.

     Bartholomeeusen K, Xiang Y, Fujinaga K, Peterlin BM · J Biol Chem 2012
     used by HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less, How P-TEFb gets out of the reservoir: a dephosphorylation, a dissociation, and a reassembly on whichever scaffold is waiting, Raising HEXIM1 to brake the fusion's output without touching the fusion - one supporting experiment, one chemical series, and no therapeutic window
325. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22623725
     MLL1, a H3K4 methyltransferase, regulates the TNFα-stimulated activation of genes downstream of NF-κB.

     Wang X, Zhu K, ... Wu M · Journal of Cell Science 2012
     used by IKK/NF-kB retains MLL on chromatin — BOTH the fusion and wild-type MLL, at two promoters, in mouse myeloid AML, and it is occupancy loss rather than protein loss
326. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22286061
     Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.

     Schwartzentruber J, Korshunov A, Liu XY, et al. · Nature 2012
     used by In pancreatic neuroendocrine tumours MEN1 and DAXX/ATRX are the two commonest mutations of the same tumour - and both are LOST there while leukaemia needs both intact
327. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23014531
     Antibody-dependent cell-mediated cytotoxicity overcomes NK cell resistance in MLL-rearranged leukemia expressing inhibitory KIR ligands but not activating ligands.

     Chan WK, Kung Sutherland M, Li Y, Zalevsky J, Schell S, Leung W · Clin Cancer Res 2012
     used by In this fusion family, MHC class I is not silenced - it is elevated and load-bearing, holding NK cells off the leukaemia stem cell, Raising MHC class I is not a free good: the same molecule is the inhibitory ligand that holds NK cells off, and in this fusion family it is an in vivo leukaemia dependency, The missing measurement: is MHC class I bivalent, does a menin inhibitor raise it, and does raising it cost NK control - in a KMT2A-rearranged cell, for the first time, The NK cell - the effector arm of haploidentical transplant, the one this disease is documented to evade, and the cell CLEC12A was named on, Which immune-evasion routes are actually documented in KMT2A-rearranged disease, and which are borrowed from AML and assumed - a ranked ledger with the bounded absences that define it
328. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22286128
     Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia

     Grembecka J, He S, Shi A, et al., Cierpicki T · Nature Chemical Biology 2012
     used by Jolanta Grembecka & Tomasz Cierpicki (University of Michigan) — the chemistry that made the menin interface druggable, KOPN-8 (CVCL_1866): the field's default KMT2A::MLLT1 line, and its fusion protein has no YEATS domain, Menin dependence of KMT2A::MLLT1: real, repeatedly demonstrated, and always as one lane of a partner panel
329. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22936661
     Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia

     Shi A, Murai MJ, He S, et al., Grembecka J, Cierpicki T · Blood 2012
     used by Jolanta Grembecka & Tomasz Cierpicki (University of Michigan) — the chemistry that made the menin interface druggable, KMT2B, AFF2, AFF3, AFF4 and ENL carry most of the contact residues of the two interfaces the fusion keeps (menin-KMT2A and AF9-AFF1), so a substitute is structurally possible and selectivity cannot be read from either surface; at the menin side KMT2B differs at W7
330. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3U85: Crystal structure of human menin in complex with MLL1

     Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X, Lei M · RCSB Protein Data Bank 2012
     used by JUND - the AP-1 subunit menin holds down, and the one a menin inhibitor lets go, Menin-JunD: the same pocket, the same drug, the opposite job
331. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23166019
     Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

     Herz HM, Mohan M, Garruss AS, Liang K, Takahashi YH, Mickey K, Voets O, Verrijzer CP, Shilatifard A · Genes & Development 2012
     used by KDM6A / UTX — a commonly asserted KMT2A partner that belongs to a different complex and points the opposite way
332. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22581003
     Molecular characterization of identical, novel MLL-EPS15 translocation and individual genomic copy number alterations in monozygotic infant twins with acute lymphoblastic leukemia.

     Kotecha RS, Ford J, Beesley AH, Anderson D, Cole CH, Kees UR · Haematologica 2012
     used by KMT2A::EPS15 (MLL-AF1p), t(1;11)(p32;q23) — the infant-ALL cytoplasmic partner
333. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22854283
     Molecular identification of a new splicing variant of the MLL - MLLT11 fusion transcript in an adult with acute myeloid leukemia and t(1;11)(q21;q23).

     Lee S, Park TS, Yang JJ, Oh SH, Cho EH, Lee S, et al. · Acta Haematol 2012
     used by KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment
334. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22682626
     A three-way translocation of MLL, MLLT11, and the novel reciprocal partner gene MYO18A in a child with acute myeloid leukemia.

     Ussowicz M, Jaśkowiec A, Meyer C, Marschalek R, Chybicka A, Szczepański T, et al. · Cancer Genet 2012
     used by KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment
335. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23007389
     The Nup153-Nup50 protein interface and its role in nuclear import.

     Makise M, Mackay DR, Elgort S, Shankaran SS, Adam SA, Ullman KS · J Biol Chem 2012
     used by KPNA2 / importin-alpha-1 (P52292) - the classical NLS receptor in the pan-MLL-fusion core, and the ONLY karyopherin of any kind in the whole 960-protein network, NUP50 / Npap60 (Q9UKX7) - a MOBILE nuclear-basket nucleoporin in the pan-MLL-fusion core, and the evidence says basket, not nuclear envelope
336. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22431598
     Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.

     Maurer T, Garrenton LS, Oh A, Pitts K, Anderson DJ, Skelton NJ, Fauber BP, Pan B, Malek S, Stokoe D, Ludlam MJ, Bowman KK, Wu J, Giannetti AM, Starovasnik MA, Mellman I, Jackson PK, Rudolph J, Wang W, Fang G · Proc Natl Acad Sci U S A 2012
     used by KRAS - the commonest co-mutation in a disease that has almost none, and it is usually in a minority of the cells
337. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22865833
     Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism.

     Alazami AM, Al-Owain M, Alzahrani F, Shuaib T, Al-Shamrani H, Al-Falki YH, Al-Qahtani SM, Alsheddi T, Colak D, Alkuraya FS · Hum Mutat 2012
     used by LARP7 - the clamp on the 3' end of 7SK, whose human loss-of-function phenotype is dwarfism and intellectual disability rather than cancer
338. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22685031
     Lineage switch in childhood acute leukemia: an unusual event with poor outcome

     Rossi JG, Bernasconi AR, Alonso CN, Rubio PL, Gallego MS, et al. · American Journal of Hematology 2012
     used by Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Lineage switch in KMT2A-rearranged leukemia — the same clone changes what kind of blood cell it is
339. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22570686
     Overexpression of the catalytically impaired Taspase1 T234V or Taspase1 D233A variants does not have a dominant negative effect in T(4;11) leukemia cells

     Bier C, Hecht R, Kunst L, Scheiding S, Wunsch D, Goesswein D, Schneider G, Krmer OH, Knauer SK, Stauber RH · PLoS ONE 2012
     used by Lost from the KMT2A half: both taspase1 cleavage sites (D2666 and D2718) - the fusion is never processed, Taspase1 is what turns the reciprocal product into an oncoprotein - and it is a conditional oncogene because of it
340. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22665483
     Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases

     Dharmarajan V, Lee JH, Patel A, Skalnik DG, Cosgrove MS · Journal of Biological Chemistry 287(33):27275-27289 2012
     used by Lost from the KMT2A half: the WIN motif and the whole WRAD interface (aa 3762-3767, Arg3765), WDR5 WIN site and KMT2A Arg3765: measured at 1.7 uM, three co-crystals, and absent from every leukaemic fusion - plus the MLL3 peptide that binds it 51-fold tighter, What was searched for a structure and what came back empty: the KMT2A interface layer enumerated by accession pair, with the graph's own unmapped interfaces listed
341. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3U85: Crystal structure of human menin in complex with MLL1

     Huang J, Gurung B, Wan B, et al. · RCSB Protein Data Bank 2012
     used by MBM2, the second menin-binding motif of KMT2A (residues 23-40): 26-fold weaker than MBM1, never separately co-crystallised, and the only part of the menin grip a drug is not aimed at
342. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3U88: Crystal structure of human menin in complex with MLL1 and LEDGF

     Huang J, Gurung B, Wan B, et al. · RCSB Protein Data Bank 2012
     used by MBM2, the second menin-binding motif of KMT2A (residues 23-40): 26-fold weaker than MBM1, never separately co-crystallised, and the only part of the menin grip a drug is not aimed at, The menin acidic shelf, Glu366-Asp370-Val371: the counter-charge that MBM2 binds, resolved in 3U88 after all - and the one patch where the drug pocket, the SvID and the gamma-H2A.X motif all touch, The menin side of the LEDGF clamp: residues 91-105 and 209-212, on the opposite face of menin from the drug pocket and 26-38 A from every other surface in this beat
343. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22544066
     Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration.

     Perciavalle RM, et al. · Nat Cell Biol 2012;14:575-83 2012
     used by MCL1 - named in 34 entries of this graph with no entry of its own until now; a mitochondrial survival protein high in infant KMT2A-rearranged ALL, druggable, and so far undruggable in patients
344. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22761769
     Novel fusion of MYST/Esa1-associated factor 6 and PHF1 in endometrial stromal sarcoma

     Panagopoulos I, Micci F, Thorsen J, Gorunova L, et al. · PLoS One 2012
     used by MEAF6 - a 191-residue subunit shared between the NuA4/TIP60 and MOZ/MORF acetyltransferase complexes, whose only two UniProt localisations both cite papers that are not localisation studies, PHF1 (PCL1) - the PRC2 accessory subunit whose Tudor domain reads H3K36me3, and the 3' acceptor shared by three different NuA4-donor fusions in two different tumour types
345. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22553314
     EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs.

     Bindels EM, Havermans M, Lugthart S, Erpelinck C, Wocjtowicz E, Krivtsov AV, Rombouts E, Armstrong SA, et al. · Blood 119:5838-5849 2012
     used by MECOM (EVI1) - a cell-of-origin memory that MLL-AF9 maintains but cannot install, present in about 43% of MLL-rearranged AML and marking the chemoresistant half
346. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22166975
     Glucose-mediated repression of menin promotes pancreatic beta-cell proliferation.

     Zhang H, Li W, Wang Q, Wang X, Li F, Zhang C, et al. · Endocrinology 2012
     used by Menin is a brake the beta cell releases on purpose: pregnancy and glucose both lower it
347. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22353710
     miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia

     Li Z, Huang H, Chen P, He M, Li Y, Arnovitz S, Jiang X, He C, Hyjek E, Zhang J, Zhang Z, Elkahloun A, Cao D, Shen C, Wunderlich M, Wang Y, Neilly MB, Jin J, Wei M, Lu J, Valk PJM, Delwel R, Lowenberg B, Le Beau MM, Vardiman J, Mulloy JC, Zeleznik-Le NJ, Liu PP, Zhang J, Chen J · Nature Communications 3:688 2012
     used by miR-196b — the HOXA-cluster microRNA that is a direct KMT2A-fusion target and a genuine double agent
348. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 23211007
     Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse.

     Burmeister T, Molkentin M, Meyer C, et al. · Exp Hematol Oncol 2012
     used by MRD by genomic breakpoint: the only assay in this disease that is fusion-specific by construction
349. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22217495
     RT-PCR screening for ETV6-RUNX1-positive clones in cord blood from newborns in the Danish National Birth Cohort

     Olsen M, Hjalgrim H, Melbye M, Madsen HO, Schmiegelow K · Journal of Pediatric Hematology/Oncology 2012
     used by Newborn screening for leukaemia fusions: verdict NOT FEASIBLE TODAY, and the reason is arithmetic plus the absence of anything to offer a positive, What fraction of fusion-positive newborns ever get leukaemia? For ETV6::RUNX1, very few. For KMT2A, nobody knows, and the biology says the answer may be most of them
350. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22293200
     A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line.

     Godin F, Villette S, Vallée B, Doudeau M, Morisset-Lopez S, Ardourel M, Hevor T, Pichon C, Bénédetti H · Biochem Biophys Res Commun 2012
     used by NF1 - the only tumour-suppressor loss in this disease, and it is a deletion, so a mutation panel cannot see it
351. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 23175229
     NLRC5: a key regulator of MHC class I-dependent immune responses.

     Kobayashi KS, van den Elsen PJ · Nat Rev Immunol 2012
     used by NLRC5 - the MHC class I transactivator, and the route by which interferon activates class I when KMT2A and KMT2B are both gone
352. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22777353
     Histone arginine methylation keeps RUNX1 target genes in an intermediate state.

     Herglotz J, Kuvardina ON, Kolodziej S, Kumar A, Hussong H, Grez M, Lausen J · Oncogene 2012
     used by No histone-mark readout has ever been measured after perturbing ANY NuRD or Sin3 subunit in a KMT2A-rearranged cell - the two complexes whose entire job is acetylation have zero acetylation data in this disease, PRMT6 - the enzyme whose mark is MUTUALLY EXCLUSIVE with the MLL complex on the H3 tail, and which shuts HOX genes down by evicting WDR5, SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's
353. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22927245
     Loss of p53 accelerates the complications of myelodysplastic syndrome in a NUP98-HOXD13-driven mouse model

     Xu H, et al. · Blood 120(15):3089-3097 2012
     used by NUP98::HOXD13, t(2;11)(q31;p15) — the myelodysplasia fusion, and a warning against targeting p53
354. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22325352
     PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes

     Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D · Molecular Cell 45(3):344-56 2012
     used by PCGF1 — the PRC1.1 scaffold whose LOSS causes menin-inhibitor resistance, so it is a restraint on the leukaemia rather than a dependency of it, PRC1.1 — the complex this graph has been leaning on, now enumerated subunit by subunit, and the enumeration changes the conclusion, RNF2 (RING1B) — the one catalytic subunit shared by every PRC1 flavour, which is why the genetics point two ways at once, RYBP - the subunit that makes a variant PRC1 complex catalytically active, named by two entries in this graph and never written
355. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22952941
     The PICALM protein plays a key role in iron homeostasis and cell proliferation.

     Scotland PB, et al. · PLoS One 2012
     used by PICALM (CALM) - the clathrin-assembly adaptor that is the 5' partner of CALM::AF10, The non-chromatin half: CALM-AF10 breaks the cell's iron intake and the cells are chelator-sensitive in vitro - but iron restriction did not extend survival in vivo (corrected 2026-09-21)
356. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22363754
     The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice.

     Suzuki M, et al. · PLoS One 2012
     used by PICALM (CALM) - the clathrin-assembly adaptor that is the 5' partner of CALM::AF10
357. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22406621
     The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA

     Rabellino A, Carter B, Konstantinidou G, Wu SY, Rimessi A, Byers LA, Heymach JV, Girard L, Chiang CM, Teruya-Feldstein J, Scaglioni PP · Cancer Research 72:2275-84 2012
     used by PML K160 SUMOylation - the retained-portion PTM that became an approved therapy, and the benchmark every other retained site should be measured against
358. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22692509
     The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling

     Lang E, Grudic A, Pankiv S, Bruserud O, Simonsen A, Bjerkvig R, Bjoras M, Boe SO · Blood 2012
     used by PML nuclear bodies and PML::RARA — the best-worked case of a fusion destroying a nuclear compartment, and what it actually predicts for KMT2A
359. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22269951
     HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules.

     Bandyopadhyay S, Harris DP, Adams GN, Lause GE, McHugh A, Tillmaand EG, Money A, Willard B, Fox PL, DiCorleto PE · Molecular and Cellular Biology 2012
     used by PRMT5 - the type II arginine methyltransferase this graph has reached for sixteen times, whose mark on H3R2 RECRUITS WDR5 to chromatin
360. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22337994
     The mixed lineage leukemia (MLL) fusion-associated gene AF4 promotes CD133 transcription.

     Mak AB, ..., Moffat J · Cancer Res 2012
     used by PROM1 / CD133 - a direct MLL-AF4 target switched on by an intragenic H3K79me2/3 enhancer, and the one surface target in this disease with a published human-relevant kill
361. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22615581
     Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing.

     Pradeepa MM, Sutherland HG, et al. · PLoS Genet 2012
     used by PSIP1 makes two proteins and only one of them has the IBD: a p52 result is not a p75 result, and the knockout mouse removes both, The third job: LEDGF sits on transcribed gene bodies with splicing factors and changes exon choice in half the genes that have alternative isoforms
362. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22275374
     Mechanism of fragility at BCL2 gene minor breakpoint cluster region during t(14;18) chromosomal translocation

     Nambiar M, Raghavan SC · Journal of Biological Chemistry 2012
     used by RAG off-target activity: the dominant mutator in ETV6::RUNX1 ALL, and probably not the cause of KMT2A fusions
363. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22719019
     Chimeric transcript generated by cis-splicing of adjacent genes regulates prostate cancer cell proliferation

     Zhang Y, Gong M, Yuan H, Park HG, Frierson HF, Li H · Cancer Discovery 2012
     used by Read-through (cis-SAGe) chimeras: most 'fusions' called from RNA-seq in childhood ALL are normal conjoined genes
364. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22166309
     A pharmacologic inhibitor of the protease Taspase1 effectively inhibits breast and brain tumor growth

     Chen DY, Lee Y, Van Tine BA, Searleman AC, Westergard TD, Liu H, Tu HC, Takeda S, Dong Y, Piwnica-Worms DR, Oh KJ, Korsmeyer SJ, Hermone A, Gussio R, Shoemaker RH, Cheng EH, Hsieh JJ · Cancer Research 72(3):736-46 2012
     used by Reading the same-source counter-evidence: 77 notes adjudicated, and the defect is not the one the metric measures
365. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22015773
     Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia.

     Stumpel DJ, Schneider P, Seslija L, Osaki H, Williams O, Pieters R, Stam RW · Leukemia 26(4):682-692 2012
     used by Romidepsin - the HDAC inhibitor with the best preclinical case in KMT2A-rearranged INFANT ALL specifically, and a mechanism that is not about histones at all, The KMT2A-r DNA methylation signature — focal hypermethylation, no global hypomethylation, and a hypomethylating agent that did not help
366. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22325148
     RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3.

     Tavares L, Dimitrova E, Oxley D, Webster J, et al. · Cell 2012
     used by RYBP - the subunit that makes a variant PRC1 complex catalytically active, named by two entries in this graph and never written
367. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     GEO Series GSE34097 — The SEC family of RNA Polymerase II elongation factors: gene target specificity and transcriptional output

     Luo Z, Lin C, Shilatifard A · NCBI Gene Expression Omnibus 2012
     used by SEC — the AFF1/AFF4-scaffolded super elongation complex, the particle KMT2A::AFF1 is a permanent subunit of, The SEC-family target sets, reconstructed as a full three-way Venn: 27.5% of the family's transcriptional output is invisible to AFF4 depletion — and the two 'distinct' sibling sets overlap 8-20x more than chance
368. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22314233
     Structure and assembly of the SF3a splicing factor complex of U2 snRNP.

     Lin PC, Xu RM · EMBO J 2012
     used by SF3A3 / SF3a60 (Q12874) - a U2 snRNP splicing subunit in the pan-MLL-fusion core, and the paper's own named example of a NON-selective hit
369. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23250418
     Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

     Yu W, Chory EJ, Wernimont AK, et al. · Nat Commun 2012
     used by SGC0946 removes 86% of H3K79me2's share at the fusion's own sites and the four eviction quartiles are 0.1396 / 0.1453 / 0.1452 / 0.1360 - span 0.0036, Spearman +0.400, a bootstrap interval spanning zero - so a very large effect on this mark can carry no eviction-depth structure whatever
370. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 23027902
     S-nitrosylation of B23/nucleophosmin by GAPDH protects cells from the SIAH1-GAPDH death cascade.

     Lee SB, Kim CK, Lee KH, Ahn JY · J Cell Biol 2012
     used by SIAH1 — the E3 ligase that degrades AFF1, and that the reciprocal AF4::KMT2A fusion escapes
371. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22770219
     Acetylation-dependent regulation of Skp2 function.

     Inuzuka H, Gao D, Finley LW, Yang W et al. · Cell 2012
     used by SKP2 - the substrate receptor that grips the retained fragment; two nodes in this graph already pointed at it as a free-text string with nothing to point to
372. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22419068
     Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation.

     Van Aller GS, Reynoird N, et al. · Epigenetics 2012
     used by SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
373. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22641210
     The Pediatric Cancer Genome Project

     Downing JR, Wilson RK, Zhang J, Mardis ER, Pui CH, Ding L, Ley TJ, Evans WE · Nature Genetics 2012
     used by St. Jude Cloud and the Pediatric Cancer Genome Project — raw paediatric leukaemia genomes a small lab can get without a collaboration
374. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22748127
     Lens epithelium-derived growth factor deSumoylation by Sumo-specific protease-1 regulates its transcriptional activation of small heat shock protein and the cellular response.

     Ishihara K, et al. · FEBS J 2012
     used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
375. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22659140
     Tbl3 regulates cell cycle length during zebrafish development.

     Hutchinson SA, Tooke-Locke E, Wang J, Tsai S, Katz T, et al. · Dev Biol 2012
     used by TBL3 / UTP13 (Q12788) - a UTP-B ribosome-biogenesis subunit in the pan-MLL-fusion core, whose loss in zebrafish severely reduces T cells and haematopoietic stem/progenitors
376. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21921940
     The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition.

     Vilotti S, Biagioli M, Foti R, Dal Ferro M, Lavina ZS, Collavin L, et al. · Cell Death Differ 2012
     used by TDP2 - the protein-adduct remover named in this graph's own mechanism entry and until now having no entry of its own
377. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22334021
     Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse model.

     Vets S, Kimpel J, et al. · Mol Ther 2012
     used by The experiment that closes the LEDGF hole: doxycycline-inducible PSIP1 knockdown switched on AFTER a human KMT2A::AFF1 xenograft is established, The LEDGF hole, measured: every published LEDGF-removal experiment removes it BEFORE or AT transformation, and none treats an established leukaemia in an animal
378. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22396646
     LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs.

     Schrijvers R, De Rijck J, et al. · PLoS Pathog 2012
     used by The HIV field is NOT drugging LEDGF: LEDGINs and ALLINIs bind integrase, and the proof is that they still work in a LEDGF knockout cell, The paralogue that covers for LEDGF: HRP-2 carries the only other IBD in the human proteome, substitutes for LEDGF in HIV integration, and the double knockout is embryonic lethal
379. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22113294
     Affinity purification of MLL3/MLL4 histone H3K4 methyltransferase complex.

     Cho YW, Hong S, Ge K · Methods Mol Biol 2012
     used by The KMT2-family beat's own ledger: every query run, every gene dropped, every paper read and not used
380. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 23070815
     Structure and conformational change of a replication protein A heterotrimer bound to ssDNA.

     Fan J, Pavletich NP · Genes & Development 26(20):2337-47 2012
     used by The replication protein A heterotrimer (RPA1/RPA2/RPA3) - the ssDNA clamp that every resection and replication-stress claim in this corpus silently depends on, and which had no entry until cycle 160
381. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22726440
     p53 opens the mitochondrial permeability transition pore to trigger necrosis.

     Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM · Cell 2012
     used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
382. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22190735
     LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis.

     Castle CD, Cassimere EK, Denicourt C · Mol Biol Cell 2012
     used by WDR18 (Q9BV38) - the Rix1/PELP1-TEX10-WDR18 60S maturation subunit, in five MLL-fusion interactomes but NOT the index fusion's, and the block's only member whose nucleolar partitioning is SUMO-controlled
383. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21251613
     Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases.

     Xu W, Yang H, Liu Y, et al. · Cancer Cell 2011
     used by 2-hydroxyglutarate competitively inhibits the alpha-KG dioxygenases - and it hits the TET demethylases AND the KDM histone demethylases, which is why its net effect on a CXXC reader is not predictable, IDH1 - the same oncometabolite, the same assay, and NO enrichment in KMT2A-rearranged AML (6.7% vs 7.6%, p = 0.53): the control that makes the IDH2 result interpretable, IDH2 - the hypermethylating co-mutation that IS enriched in KMT2A-rearranged AML (16.0% vs 10.4%), at p = 0.0004 and not the p < 0.0001 the abstract claims, If the fusion's address requires unmethylated CpG, a hypermethylating co-mutation should be selected AGAINST - and IDH2 is selected FOR, which means the address is not the limiting resource, Put mutant IDH2 into SEM and ask three questions at once: does the unmethylated-CpG pool shrink, does the fusion move, and does its competitor move
384. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22001208
     Menin prevents liver steatosis through co-activation of peroxisome proliferator-activated receptor alpha.

     Cheng P, et al. · FEBS Lett 2011
     used by A menin inhibitor is a partial LXR agonist, and no trial in the class has looked, Menin is a corepressor of the LXR sterol sensors - one paper supplies three of this graph's twelve missing partners, and the function has never been written down here
385. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21896721
     Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes.

     Biswas D, Milne TA, Basrur V, et al. · Proc Natl Acad Sci U S A 2011
     used by AFF1 / AF4 — the 3' half of the fusion, and a target with almost no structural footing, AFF1 AF4_int motif to AF9/ENL AHD: the index fusion's only documented elongation interface, and it competes with DOT1L, Does KMT2A::AFF1 deliver DOT1L to the AHD or displace it? A competition experiment in t(4;11) cells, DOT1L leaves chromatin before menin does when the fusion is degraded, and the ordering survives a change of instrument that destroys the magnitudes - ChIP-qPCR at selected loci, target-restricted read counts and genome-wide peak presence all rank DOT1L ahead of menin while disagreeing about every number, Hypothesis: KMT2A::AFF1 does not require phase separation — recruitment biochemistry is sufficient, and the condensate model does not transfer from NUP98/ENL, Import class 2: AHD-dependent mechanism, which cannot transfer because KMT2A::AFF1 has no AHD, In KMT2A::AFF1 there is no oncogenic DOT1L unit: all H3K79 methylation is the endogenous MLLT10-directed activity, working on genes the fusion has opened, KMT2A::AFF1 has no mapped interface to DOT1L: it lacks both structurally defined recruitment modules, and the one complex-level route claimed for it is contested by reconstitution, Menin persists on chromatin after the fusion is degraded because LEDGF/PSIP1 supplies a fusion-independent tether - the authors' own proposal, never tested, and the single cheapest experiment that would change how menin displacement is interpreted as a drug readout, MLLT6 (AF17) — the fourth KMT2A fusion partner inside DotCom, and the only one no cell needs, Proximity-labelling map of KMT2A::AFF1 — the experiment nobody has run in twenty years of interactome work, Step 3 — The hijack: the fusion drags the super elongation complex to paused RNA polymerase II, Step 4 — The histone mark: DOT1L and H3K79me2/3 at fusion target genes (and why global expression barely moves), The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The order in which the fusion's programme collapses is a property of the partner, not of KMT2A - so there is no single causal chain
386. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21030982
     The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures.

     Benedikt A, Baltruschat S, Scholz B, et al. · Leukemia 2011
     used by AFF1 / AF4 — the 3' half of the fusion, and a target with almost no structural footing, Attribution audit 1 of 5 - who co-purifies with KMT2A::AFF1: the inventory does not survive, the individual partner blots mostly do, Bounded unreadable: the only affinity purification of a SET-retaining KMT2A-derived fusion complex fails all four routes, and the molecule is the reciprocal product, Enumerating the WRAD-versus-KMT2A-fusion literature: what was searched, found, rejected and could not be read, Forty-five percent of t(4;11) patients express a KMT2A fusion transcript that keeps the whole WRAD interface, What the reciprocal product assembles: P-TEFb, an H3K4 methyltransferase, an H3K79 methyltransferase, an arginine methyltransferase and an acetyltransferase
387. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21233834
     The heterodimerization domains of MLL-FYRN and FYRC--are potential target structures in t(4;11) leukemia.

     Pless B, Oehm C, Knauer S, et al. · Leukemia 2011
     used by AFF1::KMT2A (AF4-MLL), the der(4) product: what it is made of, residue by residue, FYRN/FYRC: the clip that holds the cut reciprocal protein together, and the only fusion-adjacent interface anyone has tried to break with a decoy, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: the FYRN-FYRC clamp (2018-2074 / 3666-3747) that holds wild-type KMT2A together, Lost from the KMT2A half: the transactivation domain (aa 2829-2883) and its CBP contact, SIAH1 — the E3 ligase that degrades AFF1, and that the reciprocal AF4::KMT2A fusion escapes
388. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21330300
     Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability.

     Melko M, Douguet D, Bensaid M, Zongaro S, Verheggen C, Gecz J, Bardoni B · Hum Mol Genet 2011
     used by AFF3 (LAF4) — the AFF-family scaffold of SEC-L3, and a KMT2A fusion partner in its own right, AFF4 — the textbook SEC scaffold that KMT2A::AFF1 cells need LESS than other leukemias, Hypothesis: KMT2A::AFF1 mislocalises to or disrupts nuclear speckles, and paraspeckle biology (NEAT1) is a fusion-repressed differentiation brake, Hypothesis: KMT2A::AFF1 rewires splicing, because AFF1's own protein family are G-quadruplex RNA-binding splicing modulators and the fusion keeps AFF1, Nuclear speckles — the compartment everyone assumes KMT2A::AFF1 uses, on evidence that skips AFF1 itself, The shared reader sits in a complex whose only well-defined normal job is parent-of-origin silencing — and the published safety package for YEATS inhibition is entirely haematopoietic, Three of the four AFF scaffolds have a named human Mendelian syndrome and the index fusion's partner has none — a 0/4 that is a fact about AFF1 and not about how hard anyone has looked
389. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.journal-articlePMID 20869771
     t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL

     · Leukemia Research 2011
     used by An anti-MLL-C antibody in a t(4;11) cell is looking at two proteins at once, Bounded absence: not one menin-inhibitor study, trial or preclinical paper has ever recorded reciprocal fusion status, Competing model 3: reciprocal status is a proxy for where the break fell, and the thing that changed is the DIRECT product, Competing model 4: t(4;11) cells are addicted to the direct fusion and completely indifferent to the reciprocal one, Forty-five percent of t(4;11) patients express a KMT2A fusion transcript that keeps the whole WRAD interface, Infants whose leukaemia expresses the reciprocal fusion survive far better - 62.4% versus 11.7% event-free at four years, Menin primacy was established on the der(11) product alone and has never been tested against the der(4) product, Nobody has ever stratified any KMT2A::MLLT1 outcome or drug-response analysis by reciprocal or spliced status - a measured absence, with the queries, Targeted PRM for the KMT2A::AFF1 junction peptide - the experiment that makes every other attribution claim testable
390. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21131980
     An assessment of histone-modification antibody quality.

     Egelhofer TA, Minoda A, Klugman S, Lee K, et al. · Nat Struct Mol Biol 2011
     used by An assay that cannot separate me2a from me2s cannot test the arginine switch - the two states are isobaric and predict OPPOSITE things, so a non-discriminating readout returns no information rather than an imprecise answer, Arginine methylation gates KMT2-complex access to chromatin at two residues, in both directions, independently of the menin tether AND of the WIN motif - a parallel control point, not a rival to menin dependence, H3R2me2a - the asymmetric arginine mark two residues from H3K4 that LOCKS the WRAD module off the histone tail, and the first arginine mark node in this graph
391. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21807893
     Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex.

     Rai TS, Puri A, McBryan T, et al. · Molecular and Cellular Biology 2011
     used by ASF1A - the compensating paralogue: the only gene in this beat that is not required in a single one of 1,208 cell lines, and it still has a leukaemia phenotype, CABIN1 - a 2,220-residue calcineurin inhibitor that is also a full member of the H3.3 chaperone complex, and nobody has asked which job matters in blood, HIRA - the chaperone that puts new H3.3 into transcribed gene bodies, and therefore the machine that runs this graph's clearance clock, The HUCA complex (HIRA/UBN1/CABIN1/ASF1a) - four proteins, one job: put H3.3 into chromatin without waiting for S phase
392. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21106533
     A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex.

     Patel A, Vought VE, Dharmarajan V, Cosgrove MS · Journal of Biological Chemistry 2011
     used by ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, ASH2L: the only WRAD subunit ever perturbed in a KMT2A::AFF1 cell, once, weakly, RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum
393. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21719641
     Altered telomeres in tumors with ATRX and DAXX mutations.

     Heaphy CM, de Wilde RF, Jiao Y, et al. · Science 2011
     used by Assay telomere maintenance across the thirteen B-lineage ALL DepMap lines, and see whether it predicts the DAXX dependency split, In pancreatic neuroendocrine tumours MEN1 and DAXX/ATRX are the two commonest mutations of the same tumour - and both are LOST there while leukaemia needs both intact, The DAXX requirement in B-lineage KMT2A-rearranged lines is a telomere phenotype, not a fusion-target phenotype - and the two non-KMT2A lines in the deep group are the test
394. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21741597
     MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L.

     Bernt KM, Zhu N, Sinha AU, et al. · Cancer Cell 2011
     used by At low drug doses the leukaemia dies through FLT3, not through HOXA9 - a second H3K79me2 pathway the dose-response hides, Bivalent and primed chromatin at fusion target loci — and why the H3K4/H3K27 story is weaker than usually told, H3K27me3 - the repressive mark this graph argued about for seventy-seven cycles without ever writing an entry for it, H3K4me3 - the mark KMT2A's own SET domain writes, that the fusion cannot write, that an interface in this graph already binds, and that switches PRC2 off, H3K79me2 - the di-methyl state the leukaemia actually runs on, and the one menin turns out to govern only half of, Import class 1: murine MLL-AF9 myeloid transformation, the field's default assay and this graph's largest single import, Kathrin Bernt (University of Pennsylvania / Children's Hospital of Philadelphia) — DOT1L and H3K79 methylation in KMT2A-rearranged leukemia, Mechanism class 1 — chromatin and elongation hijack (KMT2A-r, NUP98-r), On the absolute scale the H3K79me2 gradient is real and it runs the other way from the share: the most heavily marked decile retains 0.8% and the least marked retains 31%, a 41-fold gradient - and every decile, in both lines and under both drugs, still loses, Step 4 — The histone mark: DOT1L and H3K79me2/3 at fusion target genes (and why global expression barely moves), The chain's biggest risk is generalising a myeloid mouse result to infant B-ALL, and the graph cannot measure how much of it does, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The same baseline-matched test that kills the target effect under EPZ5676 fires hard under compound 10 - at d6 and d9, in both cell lines, 4 of 4 contrasts (p = 0.0012 to <0.0001) - and in MOLM13 HOXA9 holds 24.5% of its H3K79me2 where the genome median holds 4.5%, Two inhibitors of the same DOT1L active site leave different residual H3K79me2 landscapes, and the difference sits at the KMT2A-fusion target loci - so 'how much H3K79me2 is left' is a compound-specific readout, not a generic measure of DOT1L inhibition
395. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22094252
     CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis.

     Tan J, Jones M, Koseki H, et al. · Cancer Cell 2011
     used by BCOR, not CBX8, is the AHD contact MLL-AF9 cannot lose - and the same two partners bind ENL far more tightly than AF9, CBX8 — the one place in this interactome where two good papers flatly disagree, and DepMap takes a side, Polycomb bodies — indirect evidence via CBX8, undercut by the finding that CBX8-PRC1 condensates are dissolved rather than built by the rest of PRC1, Polycomb in KMT2A-r leukemia — core PRC2 required, EZH2 and BMI1 dispensable, and CBX8 acting outside its repressive role
396. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21555454
     The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3.

     Rahman S, Sowa ME, Ottinger M, Smith JA, Shi Y, Harper JW, Howley PM · Mol Cell Biol 2011
     used by BICRA (GLTSCR1) - the ncBAF scaffold, zero PubMed records in KMT2A leukaemia, and a lineage-independent dependency in KMT2A-rearranged lines
397. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21624810
     Functional crosstalk between Bmi1 and MLL/Hoxa9 axis in establishment of normal hematopoietic and leukemic stem cells

     Smith LL, Yeung J, Zeisig BB, Popov N, Huijbers I, Barnes J, Wilson AJ, Taskesen E, Delwel R, Gil J, Van Lohuizen M, So CW · Cell Stem Cell 8:649-662 2011
     used by BMI1 - the self-renewal gene that KMT2A fusions can do without, because HOXA9 covers for it at the same locus, BMI1, CDKN2A and CDK6 are one circuit, not three genes - and in KMT2A-rearranged disease it has a loop nobody has measured, Does a menin inhibitor create a BMI1 dependency? A two-arm knockout-under-drug experiment in KMT2A::AFF1 cells, with the CDKN2A readout that decides the mechanism, If HOXA9 substitutes for BMI1 at CDKN2A, then a menin inhibitor should CREATE a BMI1 dependency that does not exist at baseline, Polycomb in KMT2A-r leukemia — core PRC2 required, EZH2 and BMI1 dispensable, and CBX8 acting outside its repressive role
398. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21527932
     Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells

     Yuan J, Takeuchi M, Negishi M, Oguro H, Ichikawa H, Iwama A · Leukemia 25:1335-1343 2011
     used by BMI1 - the self-renewal gene that KMT2A fusions can do without, because HOXA9 covers for it at the same locus, If HOXA9 substitutes for BMI1 at CDKN2A, then a menin inhibitor should CREATE a BMI1 dependency that does not exist at baseline
399. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21389315
     Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia

     Montes R, Ayllon V, Gutierrez-Aranda I, Prat I, Hernandez-Lamas MC, Ponce L, Bresolin S, te Kronnie G, Greaves M, Bueno C, Menendez P · Blood 2011
     used by Bone marrow haematopoietic stem cell — the postnatal comparator, and why the same fusion behaves differently here, Fetal liver haematopoietic stem and progenitor cell — the leading candidate cell of origin for t(4;11) infant ALL, The stem-like self-renewal state — a limited stem-cell module grafted onto a committed cell
400. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21964340
     Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia.

     Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, et al. · Nature 478(7370):529-533 2011
     used by BRD3 - named in the founding BET paper's own mechanism and in one title since, and not once separated from BRD4 by any experiment in this disease, BRD4 — the best-drugged protein in this beat, and the one whose clinical result is already in and disappointing
401. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21814200
     RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia.

     Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al., Lowe SW, Vakoc CR · Nature 2011
     used by BRD4 — the best-drugged protein in this beat, and the one whose clinical result is already in and disappointing
402. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21681188
     The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice.

     Deshpande AJ, et al. · Leukemia 2011
     used by CALM-AF10 reaches DOT1L through exactly the same OM-LZ interface as KMT2A::MLLT10 - the recruitment transfers, the addressing does not, PICALM / CALM - domain architecture, residue coordinates, and which parts the fusion keeps, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A
403. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21289070
     DOT1L regulates dystrophin expression and is critical for cardiac function.

     Nguyen AT, Xiao B, Neppl RL, Kallin EM, Li J, Chen T, et al., Zhang Y · Genes Dev 2011
     used by Cardiomyocyte - the non-haematopoietic cell that two of this graph's drug targets are required in, which makes it the graph's clearest bystander-organ liability
404. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21499536
     CD34 Antigen: Determination of Specific Sites of Phosphorylation In Vitro and In Vivo.

     Deterding LJ; Williams JG; Humble MM; Petrovich RM; Wei SJ; Trempus CS; Gates MB; Zhu F; Smart RC; Tennant RW; Tomer KB · Int J Mass Spectrom 2011
     used by CD34 - named in 132 entries of this graph and written in none, and it does not mean what the graph has been using it to mean
405. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21221636
     Absence of nucleolar parafibromin immunoreactivity in subsets of parathyroid malignant tumours.

     Juhlin CC, Haglund F, Obara T, Arnold A, Larsson C, Höög A · Virchows Arch 2011
     used by CDC73 / parafibromin — the PAF1C subunit that was genetically tested, and a second tumour suppressor required by the fusion
406. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22012619
     The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes.

     Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinkova P, Luo Z, Cimermancic P, Ule J, Peterlin BM · Genes Dev 2011
     used by CDK12 - a different kinase with a different cyclin, and in KMT2A-rearranged lines it is an anti-dependency, CDK13 - rank 171 of 17,728, equally deep in both lineage halves, and essentially unstudied in leukaemia, Knock down CDK13 and CDK12 side by side in lineage-matched KMT2A and non-KMT2A lines, and ask whether the DepMap signal is real, The transcriptional CDK with a real KMT2A-rearranged selectivity signal is CDK13, not CDK9 - and nobody has looked
407. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21551233
     Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study.

     Coenen EA, Raimondi SC, et al. · Blood 2011
     used by Children's Cancer Hospital Egypt (n=150 KMT2A-r): EFS 50% to 17% across four partner groups in a single-centre cohort
408. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21962511
     Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells

     Chiarle R, Zhang Y, Frock RL, Gostissa M, Alt FW, et al. · Cell 2011
     used by Class switch recombination: a B cell deliberately mutates and cuts its own antibody locus, and the same enzyme causes MYC-IgH translocations
409. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21962510
     Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes

     Klein IA, Resch W, Jankovic M, Robbiani DF, Casellas R, Nussenzweig MC, et al. · Cell 2011
     used by Class switch recombination: a B cell deliberately mutates and cuts its own antibody locus, and the same enzyme causes MYC-IgH translocations
410. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20952059
     Significance of AF4-MLL reciprocal fusion in t(4;11) leukemias?

     Sanders DS, Muntean AG, Hess JL · Leuk Res 2011
     used by Competing model 4: t(4;11) cells are addicted to the direct fusion and completely indifferent to the reciprocal one
411. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21277021
     Authors' comments: t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL.

     Kumar AR, Yao Q, Li Q, et al. · Leuk Res 2011
     used by Competing model 4: t(4;11) cells are addicted to the direct fusion and completely indifferent to the reciprocal one
412. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21990363
     An environment-dependent structural switch underlies the regulation of carnitine palmitoyltransferase 1A.

     Rao JN, Warren GZL, Estolt-Povedano S et al · Journal of Biological Chemistry 2011
     used by CPT1A - the outer-mitochondrial-membrane fatty-acid gatekeeper that is also a lysine succinyltransferase, fused to KMT2A exon 3 in the one case that is tether WITHOUT address
413. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21873227
     Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin.

     He N, Chan CK, Sobhian B, Chou S, Xue Y, Liu M, Alber T, Benkirane M, Zhou Q · Proceedings of the National Academy of Sciences USA 2011
     used by CTR9 — a PAF1C subunit the field assumes is a fusion partner, with no paper that tested it, ELL2 — a SEC subunit that almost no cell needs, next to a paralogue almost every cell needs, KMT2A::ELL (MLL-ELL), t(11;19)(q23;p13.1)
414. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21518888
     Down-regulation of homeobox genes MEIS1 and HOXA in MLL-rearranged acute leukemia impairs engraftment and reduces proliferation

     Orlovsky K, Kalinkovich A, Rozovskaia T, et al. · Proc Natl Acad Sci U S A 2011
     used by CXCL12 (SDF-1) - the marrow retention chemokine this graph already had a mechanism entry for and no entry for the protein, CXCR4 - named in eighteen entries of this graph with no entry of its own, and the one niche molecule with a drug, a paediatric trial and a direct KMT2A-r experiment, CXCR4 function in KMT2A-rearranged blasts is an output of the fusion's own HOXA/MEIS1 program, so a menin inhibitor should switch off the niche axis without a CXCR4 antagonist, Niche biology HAS been measured in KMT2A-rearranged disease - but in the index fusion itself there is essentially one marrow-niche molecular experiment, from 2011, Nobody has reported what a menin inhibitor does to CXCR4: zero papers name menin and CXCR4 together, and the RNA-seq that would answer it is already public
415. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21460035
     The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity.

     Kappes F, Waldmann T, Mathew V, Yu J, Zhang L, Khodadoust MS, Chinnaiyan AM, Luger K, Erhardt S, Schneider R, Markovitz DM · Genes and Development 2011
     used by DEK - a chromatin architectural protein that gatekeeps H3.3 and boosts HP1alpha, is a fusion partner in its own right, and is the substrate behind this graph's third CK2 route
416. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21163962
     Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation.

     Song J, Rechkoblit O, et al. · Science 2011
     used by DNMT1 - the antagonist: its CXXC domain reads unmethylated CpG in order to STOP methylation, and it is the only heterologous CXXC that runs an MLL-AF9 leukaemia
417. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21726816
     The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation.

     Wu L, Zee BM, Wang Y, Garcia BA, Dou Y · Mol Cell 2011
     used by Does the fusion carry an H2B ubiquitin ligase? A co-IP and an H2BK34ub CUT&RUN in KMT2A::AFF1 cells, H2BK34ub — a second ubiquitination site on H2B that also stimulates DOT1L, written by MSL1/MSL2, and important at HOXA9 and MEIS1, MSL1 - the MSL scaffold that carries MOF and MSL2 to HOXA9 and MEIS1, with zero records against KMT2A and a mapped, drawable domain architecture, MSL2 — the second H2B ubiquitin ligase, sitting inside the MOF complex the KMT2A fragment contacts, The fusion may reach the H2B ubiquitin mark through MOF-MSL rather than through RNF20/RNF40 — the one configuration in which this layer could be selective, The H2BK34ub HOXA9/MEIS1 result is HeLa: the full text contains the word leukaemia zero times
418. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22087315
     AF17 facilitates Dot1a nuclear export and upregulates ENaC-mediated Na+ transport in renal collecting duct cells.

     Wu H, Chen L, Zhou Q, Zhang W · PLoS One 2011
     used by DOT1L's localization record is a mouse kidney paper wearing a human label - and the one image of it in a leukaemia cell is a supporting figure a title search cannot see, MLLT6 (AF17) — the fourth KMT2A fusion partner inside DotCom, and the only one no cell needs
419. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21325596
     Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions.

     Quentin S, Cuccuini W, et al. · Blood 2011
     used by Eleven immortalised lines passaged for decades: the competing explanation this beat could not close
420. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20854876
     MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia.

     Monroe SC, Jo SY, Sanders DS, et al. · Exp Hematol 2011
     used by ELL — rank 7 on selectivity and the deepest common-essential in the top ten, with one NMR fragment to its name
421. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21832080
     The eleven-nineteen lysine-rich leukemia gene (ELL2) influences the histone H3 protein modifications accompanying the shift to secretory immunoglobulin heavy chain mRNA production.

     Milcarek C, Albring M, Langer C, et al. · J Biol Chem 2011
     used by ELL — rank 7 on selectivity and the deepest common-essential in the top ten, with one NMR fragment to its name, ELL2 — a SEC subunit that almost no cell needs, next to a paralogue almost every cell needs
422. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22153374
     ELP3 controls active zone morphology by acetylating the ELKS family member Bruchpilot.

     Miśkiewicz K, Jose LE, et al. · Neuron 2011
     used by ELP3 - the catalytic subunit, the only Elongator protein with a real acetyltransferase domain, and the one whose loss in mouse blood causes marrow failure and then p53-mutant leukaemia
423. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21673349
     Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice

     Ng AP, Loughran SJ, Metcalf D, Hyland CD, de Graaf CA, Hu Y, Smyth GK, Hilton DJ, et al. · Blood 118:2454-2461 2011
     used by ERG - a heptad stem-cell transcription factor whose 15 mentions in this graph are mostly about OTHER diseases, and whose best-established role in B-ALL is loss of function, not cooperation
424. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22037578
     Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs.

     Taguchi R, Yamada M, Horiguchi K, Tomaru T, Ozawa A, Shibusawa N, Hashimoto K, Okada S, Satoh T, Mori M · Biochem Biophys Res Commun 2011
     used by Experiment: read the endocrine limb and the marrow limb of menin-MLL in the SAME animals at the SAME exposure, MEN1 / menin — the adaptor the fusion cannot work without, The tissue selectivity of MEN1 syndrome is not in MEN1: menin is expressed evenly everywhere and MLL, p27 and p18 are the endocrine-predominant ones
425. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21962897
     FOXP1 and PAX5 are rare but recurrent translocations partners in acute lymphoblastic leukemia

     Put N, Deeren D, Michaux L, Vandenberghe P · Cancer Genet 2011
     used by FOXP1 - the forkhead repressor that licenses the pro-B to pre-B transition and blocks apoptosis with NF-kB, sitting at a 105x MLL1-N bin in a leukaemia whose defining lesion is a pro-B arrest
426. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 22195017
     The human nucleolar protein FTSJ3 associates with NIP7 and functions in pre-rRNA processing.

     Morello LG, Coltri PP, Quaresma AJ, Simabuco FM, Silva TC, Singh G, Nickerson JA, Oliveira CC, Moore MJ, Zanchin NI · PLoS One 2011
     used by FTSJ3 (Q8IY81) - the pre-rRNA 2'-O-methyltransferase at the weakest edge of the MLL-fusion nucleolar block: two baits of seven, not the index fusion, and never screened
427. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22042975
     Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region

     Ivanovs A, Rybtsov S, Welch L, Anderson RA, Turner ML, Medvinsky A · Journal of Experimental Medicine 2011
     used by Haemogenic endothelium — the vessel-wall cell that gives birth to blood
428. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21258344
     Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes.

     Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G · Nature Biotechnology 2011
     used by HDAC1 and HDAC2 belong to at least five different corepressor complexes, so an HDAC1/2 observation names no complex - and this graph carried both enzymes without the scaffolds that would tell them apart, SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's
429. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21907836
     Interactome study suggests multiple cellular functions of hepatoma-derived growth factor (HDGF).

     · J Proteomics 2011
     used by HDGF - the third PWWP paralogue, which pulls down LEDGF but has the reader domain WITHOUT the domain that grips MLL
430. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21460244
     3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice.

     Ikeda K, Mason PJ, et al. · Blood 2011
     used by HMGA2 (P52926) - a direct KMT2A::AFF1 target through the let-7b axis, and a recurrent fusion partner whose own fusions work by escaping a microRNA rather than by making a chimeric protein
431. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21423168
     A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression

     Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY · Nature 472(7341):120-4 2011
     used by HOTTIP lncRNA — the 5' HOXA switch that holds the leukemic chromatin domain open
432. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21471217
     HoxA10 activates CDX4 transcription and Cdx4 activates HOXA10 transcription in myeloid cells

     Bei L, Huang W, Wang H, Shah C, Horvath E, Eklund E · Journal of Biological Chemistry 286:19047-19064 2011
     used by HOXA10 - named in 27 entries as part of the HOXA output and never written; a posterior HOX paralogue that is regulated with HOXA9 and tested far less often
433. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21613260
     Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment.

     Goto E, Tomita A, Hayakawa F, Atsumi A, Kiyoi H, Naoe T · Blood 2011
     used by Hypothesis — forced-oligomerisation interfaces are the mutation-resistant drug targets the fusion field has been ignoring, PML::RARA, t(15;17)(q24;q21), Why PML::RARA became curable — and what KMT2A::AFF1 does not share with it
434. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21414819
     Identification of characteristic IGF2BP expression patterns in distinct B-ALL entities

     Stoskus M, et al. · Blood Cells Mol Dis 2011
     used by Hypothesis: IGF2BP2 and IGF2BP3 buffer each other in KMT2A::AFF1 leukaemia, so single-gene CRISPR under-reports both, I3IN-002 — the first small-molecule IGF2BP3 inhibitor with in vivo activity in an MLL-Af4 model, IGF2BP1 — the IMP paralogue that belongs to a DIFFERENT fusion, and the cleanest control the family offers, IGF2BP2 — the paralogue co-over-expressed with IGF2BP3 in MLL/AF4 B-ALL, and the one with an inhibitor in another leukaemia, The decisive experiment: acute degron removal of IGF2BP3, IGF2BP2 and both, read on self-renewal and xenograft initiation rather than bulk dropout, The RNA layer scored for KMT2A-selectivity across 79 genes, lineage-split — PTBP1 is the only menin-shaped hit, and the IGF2BP family shows no co-dependency
435. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 21714766
     MLL-SEPTIN gene fusions in hematological malignancies.

     Cerveira N, Bizarro S, Teixeira MR · Biol Chem 2011
     used by Hypothesis: tubulin/microtubule association is a recurrent, unnamed property of the KMT2A partners whose transforming module has no other assignment, Non-elongation KMT2A partners considered and not written: what the searches actually returned, partner by partner, SEPTIN2 (septin-2 / NEDD5) — KMT2A fusion partner in t(2;11)(q37;q23)
436. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21670200
     Proteolytically cleaved MLL subunits are susceptible to distinct degradation pathways

     Yokoyama A, Ficara F, Murphy MJ, Meisel C, Naresh A, Kitabayashi I, Cleary ML · Journal of Cell Science 124(Pt 13):2208-2219 2011
     used by Hypothesis: what the KMT2A half loses is control of its own abundance, not control of its activity, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: the FYRN-FYRC clamp (2018-2074 / 3666-3747) that holds wild-type KMT2A together
437. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21252315
     DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.

     Jiao Y, Shi C, Edil BH, et al. · Science 2011
     used by In pancreatic neuroendocrine tumours MEN1 and DAXX/ATRX are the two commonest mutations of the same tumour - and both are LOST there while leukaemia needs both intact
438. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21892841
     JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth.

     Zouein FA, Duhé RJ, Booz GW · Growth Factors 2011
     used by JAK1 - recruited and stabilised by AF10 fusions, and the kinase whose downstream STAT1 the class I effect of menin inhibition explicitly does not need
439. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21953510
     Clinical outcome and monitoring of minimal residual disease in patients with acute lymphoblastic leukemia expressing the MLL/ENL fusion gene.

     Elia L, Grammatico S, Paoloni F, et al. · American Journal of Hematology 2011
     used by KMT2A::MLLT1 outcome by age band: favourable in adult ALL, high-risk in childhood AML, and completely unstratified in the infants who are most of the disease
440. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21620472
     The t(11;19)(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukemias.

     Duhoux FP, Ameye G, Libouton J, Bahloula K, Iossifidis S, Chantrain CF, et al. · Leuk Res 2011
     used by KMT2A::MYO1F, t(11;19)(q23;p13.2) — recurrent in infant AML, and never functionally tested, MYO1F — unconventional myosin IF, a KMT2A partner with neither a transactivation domain nor a dimerisation domain, The deferred KMT2A partners: what the counts actually are, what was written, what was rejected, and three numbers the previous enumeration got wrong
441. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21205756
     Prognostic importance of histone methyltransferase MLL5 expression in acute myeloid leukemia.

     Damm F, Oberacker T, Thol F, et al. · J Clin Oncol 2011
     used by KMT2E (MLL5) - the family member with a dead SET domain, and the exclusion from COMPASS is justified
442. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21741596
     Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor.

     Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, et al. · Cancer Cell 2011
     used by KOPN-8 (CVCL_1866): the field's default KMT2A::MLLT1 line, and its fusion protein has no YEATS domain
443. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21474181
     Pre-natal, clonal origin of t(1;11)(p32;q23) acute lymphoblastic leukemia in monozygotic twins

     Kotecha RS, Murch A, Kees U, Cole CH · Leukemia Research 2011
     used by Latency: months from the fusion forming in a fetus to leukaemia in an infant, against years or a decade for every other backtracked fusion, Twin concordance: near-total for infant KMT2A-rearranged leukaemia, about 5% for childhood ALL overall
444. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22118463
     Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.

     Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, Iliopoulos D, Gregory RI · Cell 2011
     used by let-7 microRNA family (12 HGNC loci) - the effector LIN28B blocks. CORRECTED IN-SESSION: the headline 'zero papers in KMT2A leukaemia' was a NAME-LIST ARTEFACT; searching MLL instead of KMT2A returns three, one of them directly on point, LIN28B has two routes - blocking let-7, and binding mRNAs directly - and in KMT2A::AFF1 every published mechanism is the direct-mRNA one (let-7 IS measured in mouse MLL-fusion AML: in-session correction), LIN28B localization - a nucleolar pool that sequesters pri-let-7, a predominantly cytoplasmic steady state with cell-cycle-dependent nuclear entry, and NO measurement in any haematopoietic cell, MYBBP1A - the let-7-independent effector through which LIN28B suppresses MLL-rearranged AML, and a nucleolar MYB co-repressor that reads H3K9me2
445. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21459790
     LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

     Malumbres R, Fresquet V, Roman-Gomez J, Bobadilla M, Robles EF, Altobelli GG, Calasanz MJ, Smeland EB, et al. · Haematologica 96:980-986 2011
     used by LMO2 (rhombotin-2) - a bridging LIM-only protein, higher in pro-B and MLL-rearranged B-ALL, anti-selective in KMT2A-rearranged lines, and a physical partner of the KDM5A module that NUP98::KDM5A retains
446. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21362551
     Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein.

     Katoh Y, Ikura T, Hoshikawa Y, Tashiro S, Ito T, Ohta M, Kera Y, Noda T, Igarashi K · Mol Cell 2011
     used by MAT2A - the enzyme that makes the methyl donor, and the one metabolic dependency in this disease with two independent papers and a lymphoid PDX result
447. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21190993
     Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells

     Arai S, Yoshimi A, Shimabe M, Ichikawa M, Nakagawa M, Imai Y, Goyama S, Kurokawa M · Blood 117:6304-6314 2011
     used by MECOM (EVI1) - a cell-of-origin memory that MLL-AF9 maintains but cannot install, present in about 43% of MLL-rearranged AML and marking the chemoresistant half
448. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21729782
     Human mediator subunit MED26 functions as a docking site for transcription elongation factors.

     Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, Szutorisz H, Swanson SK, Martin-Brown S, Washburn MP, Florens L, Seidel CW, Lin C, Smith ER, Shilatifard A, Conaway RC, Conaway JW · Cell 2011
     used by MED26 — a common-essential Mediator subunit with a solved 87-residue domain and no ChEMBL target entity at all, The index fusion's 3' partner has ONE observed binary interaction in IntAct and forty-two residues of solved structure - every SEC contact attributed to AFF1 is an AFF4 result wearing AFF1's name
449. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21239436
     Participation of Akt, menin, and p21 in pregnancy-induced beta-cell proliferation.

     Hughes E, Huang C · Endocrinology 2011
     used by Menin is a brake the beta cell releases on purpose: pregnancy and glucose both lower it
450. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21116279
     Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale

     Stumpel DJPM, Schotte D, Lange-Turenhout EAM, Schneider P, Seslija L, de Menezes RX, Marquez VE, Pieters R, den Boer ML, Stam RW · Leukemia 2011
     used by microRNA genes silenced by CpG hypermethylation in t(4;11) infant ALL — the non-coding genome the fusion switches OFF
451. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20570349
     The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia

     Coskun E, von der Heide EK, Schlee C, Kühnl A, Gökbuget N, Hoelzer D, Hofmann WK, Thiel E, Baldus CD · Leukemia Research 35(2):208-13 2011
     used by miR-196b — the HOXA-cluster microRNA that is a direct KMT2A-fusion target and a genuine double agent
452. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21715312
     AF1q/MLLT11 regulates the emergence of human prothymocytes through cooperative interaction with the Notch signaling pathway.

     Parcelier A, Maharzi N, Delord M, Robledo-Sarmiento M, Nelson E, Belakhdar-Mekid H, et al. · Blood 2011
     used by MLLT11 / AF1q — a 90-residue protein with no chromatin domain and no oligomerisation module, KMT2A partner in t(1;11)(q21;q23)
453. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21546577
     Af17 deficiency increases sodium excretion and decreases blood pressure.

     Chen L, Wu H, Pochynyuk OM, Reisenauer MR, Zhang Z, Huang L, Zaika OL, Mamenko M, Zhang W, Zhou Q, Liu M, Xia Y, Zhang W · J Am Soc Nephrol 2011
     used by MLLT6 (AF17) — the fourth KMT2A fusion partner inside DotCom, and the only one no cell needs
454. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21217699
     Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1

     Kadlec J, Hallacli E, Lipp M, Holz H, Sanchez-Weatherby J, Cusack S, Akhtar A · Nature Structural & Molecular Biology 18(2):142-9 2011
     used by MSL1 - the MSL scaffold that carries MOF and MSL2 to HOXA9 and MEIS1, with zero records against KMT2A and a mapped, drawable domain architecture
455. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21828272
     An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance

     Zuber J, Rappaport AR, Luo W, Wang E, Chen C, Vaseva AV, Shi J, Weissmueller S, Fellmann C, Taylor MJ, Weissenboeck M, Graeber TG, Kogan SC, Vakoc CR, Lowe SW · Genes and Development 25(15):1628-40 2011
     used by MYB — rank 17 of 17,728 for KMT2A selectivity, and the only node in this beat where partial, transient suppression eradicated leukaemia without stopping normal blood production
456. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20713965
     Prevalence of t(12;21)[ETV6-RUNX1]-positive cells in healthy neonates

     Lausten-Thomsen U, Madsen HO, Vestergaard TR, Hjalgrim H, Nersting J, Schmiegelow K · Blood 2011
     used by Newborn screening for leukaemia fusions: verdict NOT FEASIBLE TODAY, and the reason is arithmetic plus the absence of anything to offer a positive, What fraction of fusion-positive newborns ever get leukaemia? For ETV6::RUNX1, very few. For KMT2A, nobody knows, and the biology says the answer may be most of them
457. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21444110
     Challenges in the use of NG2 antigen as a marker to predict MLL rearrangements in multi-center studies.

     · Leuk Res 2011
     used by NG2 in KMT2A-rearranged patients replicates in two independent TARGET profiles - 3 of 4 and 9 of 13 above the 90th percentile of everyone else - but it is bimodal, and the 552-fold median ratio I first computed is an artefact of a near-zero denominator, What an immunophenotype can and cannot tell you about a genotype - the arithmetic of a surrogate marker, worked on NG2, Which marker moves first? A re-analysis of flow files that already exist, to put an order on lineage switch
458. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21398221
     Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation.

     Jo SY, Granowicz EM, Maillard I, et al. · Blood 2011
     used by Normal blood needs DOT1L too - lose it in an adult mouse and the marrow fails within weeks
459. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21196496
     The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation

     Qiao Q, Li Y, Chen Z, Wang M, Reinberg D, Xu RM · J Biol Chem 2011
     used by NSD1 - the H3K36 dimethyltransferase whose catalytic activity a NUP98 fusion cannot do without, and which cells can otherwise lose almost for free
460. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21335236
     Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry

     Laurell E, Beck K, Krupina K, Theerthagiri G, Bodenmiller B, Horvath P, Aebersold R, Antonin W, Kutay U · Cell 144:539-50 2011
     used by NUP98 fusions retain a 469-residue FG repeat region that carries ZERO annotated modification sites - the cleanest retained-portion PTM absence in the four fusion families checked
461. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21813447
     NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern

     Hollink IH, et al. · Blood 118(13):3645-3656 2011
     used by NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation, NUP98::NSD1, t(5;11)(q35;p15.5)
462. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     A Study Of Panobinostat In Children With Refractory Hematologic Malignancies

     Therapeutic Advances in Childhood Leukemia Consortium; Novartis · ClinicalTrials.gov 2011
     used by Panobinostat - the HDAC inhibitor this graph has reasoned about for cycles without having an entry for, with strong KMT2A-rearranged xenograft activity and a terminated adult trial, Panobinostat lowers H2B ubiquitination in MLL-rearranged ALL by suppressing RNF20/RNF40/WAC — the only clinical-stage agent that reaches this axis, and its one ALL trial was stopped for lack of efficacy
463. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 22056243
     Curing APL through PML/RARA degradation by As2O3

     Lallemand-Breitenbach V, Zhu J, Chen Z, de The H · Trends in Molecular Medicine 2011
     used by PML nuclear bodies and PML::RARA — the best-worked case of a fusion destroying a nuclear compartment, and what it actually predicts for KMT2A
464. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21502956
     Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.

     Lehmann S, Ravn A, Carlsson L, et al. · Leukemia 2011
     used by PML::RARA, t(15;17)(q24;q21), Why PML::RARA became curable — and what KMT2A::AFF1 does not share with it
465. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21148297
     A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action.

     Chen XW, Leto D, Xiong T et al · Molecular Biology of the Cell 2011
     used by RALGAPA2 (AS250) - the catalytic brake on RalA that behaves as a tumour suppressor, fused to KMT2A exon 22 in an osteosarcoma and predicted out of frame, which makes allele DISRUPTION the better hypothesis than a chimera
466. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21764752
     The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation

     Wang L, Gural A, Sun XJ, et al., Roeder RG, Nimer SD · Science 333(6043):765-9 2011
     used by Ranked against four fusion families, the KMT2A acetylation site is the only candidate with no evidence on the fusion at all - and the strongest argument for it is one nobody has made, RUNX1 K43 acetylation - a retained-portion site that AML1-ETO genuinely requires, in the 5' partner, with the 3' partner supplying the acetyltransferase in trans, The partner, not the site, is what could make a retained KMT2A modification fusion-specific - the AML1-ETO mechanism asked of KMT2A::AFF1
467. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 21125401
     Overexpression of the EZH2, RING1 and BMI1 genes is common in myelodysplastic syndromes: relation to adverse epigenetic alteration and poor prognostic scoring.

     Xu F, Li X, Wu L, Zhang Q, Yang R, Yang Y, et al. · Ann Hematol 2011
     used by RING1 (RING1A) - the paralogue that is not RING1B, and the reason a substring search for 'RING1' in this graph returns the wrong gene
468. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21282530
     Interaction proteomics analysis of polycomb proteins defines distinct PRC1 complexes in mammalian cells.

     Vandamme J, Völkel P, Rosnoblet C, Le Faou P, Angrand PO · Mol Cell Proteomics 2011
     used by RING1 (RING1A) - the paralogue that is not RING1B, and the reason a substring search for 'RING1' in this graph returns the wrong gene
469. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21482668
     Ribosome synthesis-unrelated functions of the preribosomal factor Rrp12 in cell cycle progression and the DNA damage response.

     Dosil M · Mol Cell Biol 2011
     used by RRP12 (Q5JTH9) - a pre-40S export factor in six of seven MLL-fusion interactomes but NOT in the index fusion's, and the block's only member with a recessive human disease published in 2025
470. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21441211
     Identification of a role for histone H2B ubiquitylation in noncoding RNA 3'-end formation through mutational analysis of Rtf1 in Saccharomyces cerevisiae.

     · Genetics 2011
     used by RTF1 — the PAF1C subunit the graph was missing, on a complex that does bind the retained KMT2A fragment
471. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 22012064
     The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations.

     · Blood 2011
     used by RUNX1 — activated by KMT2A::AFF1 and then bound by the reciprocal fusion, in the one published two-oncoprotein circuit in t(4;11)
472. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21880637
     Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia.

     Wang Q, et al. · Haematologica 2011
     used by SET::NUP214 adult T-ALL is gamma-delta-lineage-restricted and resistant to steroids and chemotherapy early - the same cell state CALM-AF10 occupies
473. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21435002
     ABL1 fusion genes in hematological malignancies: a review.

     De Braekeleer E, et al. · European Journal of Haematology 2011
     used by SFPQ / PSF (P23246) - the last of 21 fusion-construct partners without an entry, and it is itself the 5' half of an ALL fusion that puts ABL1 in the nucleus
474. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21685874
     Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation.

     Bian C, Xu C, Ruan J, Lee KK, Burke TL, Tempel W, Barsyte D, Li J, Wu M, Zhou BO, Fleharty BE, Paulson A, Allali-Hassani A, Zhou JQ, Mer G, Grant PA, Workman JL, Zang J, Min J · EMBO Journal 2011
     used by SGF29 — a SAGA reader with a Tudor pocket, intermediate essentiality, and the best unexploited profile in this beat
475. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21779408
     Structural and functional profiling of the human histone methyltransferase SMYD3.

     Foreman KW, Brown M, et al. · PLoS One 2011
     used by SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
476. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21993218
     Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins.

     Duband-Goulet I, Woerner S, Gasparini S, Attanda W, Kondé E, Tellier-Lebègue C, Craescu CT, Gombault A, Roussel P, Vadrot N, Vicart P, Ostlund C, Worman HJ, Zinn-Justin S, Buendia B · Exp Cell Res 2011
     used by SREBF1 / SREBP-1 - the weakest of the three MEN1 sterol partners, because it is simultaneously the pathway's readout
477. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21393911
     CALLA negative precursor B lymphoblastic leukemia with MLL gene translocation and an unusual FISH signal pattern

     Devi SG, Goyal M, Ramakrishna NVSS, Murthy SS · Indian Journal of Pathology & Microbiology 2011
     used by Step 4: the split-signal FISH nucleus - one fusion, one green, one red
478. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21576393
     Drosophila histone locus bodies form by hierarchical recruitment of components.

     White AE, Burch BD, Yang XC, Gasdaska PY, Dominski Z, Marzluff WF, Duronio RJ · J Cell Biol 2011
     used by SUPT6H (SPT6) - the histone chaperone that rides with RNA polymerase II, which puts it closer to the fusion's proposed mechanism than anything else in this beat
479. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21504714
     Identification of the TAF15-ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12).

     Nyquist KB, Thorsen J, Zeller B, Haaland A, Troen G, Heim S, Micci F · Cancer Genet 2011
     used by TAF15 (RBP56, TAF2N) - the FET-family, prion-like partner that donates a low-complexity N-terminus to ZNF384, TAF15::ZNF384 - the FET-partner version, where the naming order in the literature is a trap and the founding experiment says the transactivation domain is not doing the work
480. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21418451
     The importin-alpha/nucleophosmin switch controls taspase1 protease function

     Bier C, Knauer SK, Docter D, Schneider G, et al. · Traffic 2011
     used by TASP1 (taspase1) - the protease that cuts KMT2A, and the timer the fusion escapes
481. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21902680
     Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols

     Andersen MK, Autio K, Barbany G, Borgstrom G, Cavelier L, Golovleva I, Heim S, Heinonen K, Hovland R, Johannsson JH, Johansson B, Kjeldsen E, Nordgren A, Palmqvist L, Forestier E · Br J Haematol 2011
     used by TCF3::PBX1 (E2A-PBX1), t(1;19)(q23;p13.3)
482. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21030584
     TDP2/TTRAP is the major 5'-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage.

     Zeng Z, Cortés-Ledesma F, El Khamisy SF, Caldecott KW · J Biol Chem 2011
     used by TDP2 - the protein-adduct remover named in this graph's own mechanism entry and until now having no entry of its own, TDP2 unglues trapped topoisomerase II from the KMT2A locus - it suppresses translocations overall and manufactures one rare junction class
483. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21765021
     Differential niche and Wnt requirements during acute myeloid leukemia progression

     Lane SW, Wang YJ, Lo Celso C, Ragu C, Bullinger L, Sykes SM, Ferraro F, Shterental S, et al. · Blood 2011
     used by The endosteal niche — the bone surface, where leukaemia-initiating cells were imaged homing and dividing symmetrically
484. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 22829076
     Resistance of MLL-AFF1-positive acute lymphoblastic leukemia to tumor necrosis factor-alpha is mediated by S100A6 upregulation.

     Tamai H, Miyake K, ... Shimada T · Blood Cancer Journal 2011
     used by TNF — the only NF-kB-activating ligand with real KMT2A::AFF1 B-ALL evidence, and the evidence says the blasts are RESISTANT to it
485. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21493871
     Multilocus association of genetic variants in MLL, CREBBP, EP300, and TOP2A with childhood acute lymphoblastic leukemia in Hispanics from Texas.

     Piwkham D, Gelfond JA, Rerkamnuaychoke B, Pakakasama S, Rebel VI, Pollock BH, et al. · Cancer Epidemiol Biomarkers Prev 2011
     used by TOP2A - the proliferation isoform, the one the drugs are actually measured against, and the only one with a germline association in this disease
486. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21317883
     53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress.

     Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B, Pedersen RS, Grøfte M, Chan KL, Hickson ID, Bartek J, Lukas J · Nat Cell Biol 2011
     used by TP53BP1 (53BP1) - the end-protection factor that decides between the two repair routes, reachable only under the wrong symbol
487. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21078665
     A small ribosomal subunit (SSU) processome component, the human U3 protein 14A (hUTP14A) binds p53 and promotes p53 degradation.

     Hu L, Wang J, Liu Y, Zhang Y, Zhang L, Kong R, Zheng Z, Du X, Ke Y · J Biol Chem 2011
     used by UTP14A (Q9BVJ6) - an SSU processome component that binds and destabilises p53, in four MLL-fusion interactomes but NOT the index fusion's and below the screen threshold
488. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21329877
     WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription.

     Zhang F, Yu X · Mol Cell 2011
     used by WAC — the adaptor that hands RNF20/RNF40 to RNA polymerase II, and the only member of this axis whose knockdown alone killed MLL-rearranged ALL cells
489. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21326211
     The SUMO system controls nucleolar partitioning of a novel mammalian ribosome biogenesis complex.

     Finkbeiner E, Haindl M, Muller S · EMBO J 2011
     used by WDR18 (Q9BV38) - the Rix1/PELP1-TEX10-WDR18 60S maturation subunit, in five MLL-fusion interactomes but NOT the index fusion's, and the block's only member whose nucleolar partitioning is SUMO-controlled
490. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21220120
     Structural and biochemical insights into MLL1 core complex assembly.

     Avdic V, Zhang P, Lanouette S, et al. · Structure 2011
     used by WDR5 and RBBP5: the second arm of the WRAD hub, RBBP5 V375-D376-V377 into the same propeller face, co-crystallised with the MLL1 WIN peptide in one structure
491. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3P4F: Structural and biochemical insights into MLL1 core complex assembly and regulation.

     Avdic V, Zhang P, Lanouette S, et al. · RCSB Protein Data Bank 2011
     used by WDR5 and RBBP5: the second arm of the WRAD hub, RBBP5 V375-D376-V377 into the same propeller face, co-crystallised with the MLL1 WIN peptide in one structure
492. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20974633
     The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering.

     Hendrix J, Gijsbers R, De Rijck J, Voet A, Hotta J, McNeely M, Hofkens J, Debyser Z, Engelborghs Y · Nucleic Acids Res 2011
     used by Where LEDGF/p75 actually is: bound to chromatin through mitosis, in the nuclear interior with H3K36me3 - and never once imaged in a KMT2A-rearranged cell
493. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21642962
     Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia.

     Puente XS, Pinyol M, Quesada V, et al. · Nature 2011
     used by XPO1 E571K: a change-of-function hot spot in the NES-binding groove - and it does NOT confer resistance to the drugs that bind the same groove, XPO1 mutation in acute leukaemia, counted with denominators and a positive control: 1 of 739 B-ALL, 0 of 584 paediatric AML, 0 of 1,103 adult AML
494. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21130701
     Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.

     Figueroa ME, Abdel-Wahab O, Lu C, et al. · Cancer Cell 2010
     used by 2-hydroxyglutarate competitively inhibits the alpha-KG dioxygenases - and it hits the TET demethylases AND the KDM histone demethylases, which is why its net effect on a CXXC reader is not predictable, IDH and TET2 mutations are mutually exclusive in AML - so 'IDH2 enriched, TET2 depleted' in one cohort is ONE observation, not two, IDH1 - the same oncometabolite, the same assay, and NO enrichment in KMT2A-rearranged AML (6.7% vs 7.6%, p = 0.53): the control that makes the IDH2 result interpretable, IDH2 - the hypermethylating co-mutation that IS enriched in KMT2A-rearranged AML (16.0% vs 10.4%), at p = 0.0004 and not the p < 0.0001 the abstract claims, If the fusion's address requires unmethylated CpG, a hypermethylating co-mutation should be selected AGAINST - and IDH2 is selected FOR, which means the address is not the limiting resource
495. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20124218
     Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial.

     Stork LC, Matloub Y, Broxson E, La M, Yanofsky R, Sather H, et al. · Blood 2010
     used by 6-Thioguanine - the drug a 1,498-child randomised trial removed from maintenance and left in intensification, which is exactly where Interfant-06 uses it
496. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21170338
     ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.

     Frietze S, et al. · PLoS One 2010
     used by A genome-wide null flatters any interval that belongs to an enriched class: the KMT2A promoter ranked in the top 0.07% of the genome and is 1.24x an ordinary housekeeping promoter, and the exon-11 element ranked in the top 3% and sits BELOW the median CTCF anchor, RUN, and the absence closes: all 13 released ENCODE BRCA1, CBX3 and CBX1 ChIP-seq tracks read at the KMT2A locus with three nulls - zero called peaks in 13 of 13, the breakpoint cluster at 0.57-1.24x the genome, and the exon-11 CTCF element BELOW the median CTCF anchor of its own cell type in 10 of 13
497. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20130599
     NF-kappaB activation mediates resistance to IFN beta in MLL-rearranged acute lymphoblastic leukemia.

     Tracey L, Streck CJ, Du Z, Williams RF, Pfeffer LM, Nathwani AC, Davidoff AM · Leukemia 2010
     used by A menin inhibitor may release RELA from menin's restraint — and released RELA is what keeps MLL fusions on chromatin. Prior 0.20, RELA (p65) — menin binds it and represses it, and it is required to keep MLL oncoproteins on chromatin, The NF-kB story in KMT2A-rearranged leukaemia is a myeloid story, and the lymphoid half is not a weaker version of it — it is a different subject
498. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20010842
     Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia.

     Cierpicki T, Risner LE, Grembecka J, et al. · Nat Struct Mol Biol 2010
     used by A tighter CXXC domain fails and a weaker one works: affinity rank does not predict function in the MLL-AF9 swap series, CXXC to unmethylated CpG DNA: nine mapped contact residues, and an affinity that spans 44 uM to 33 nM depending on the construct, the DNA and the salt, CXXC-DNA interface of the KMT2A fusion: a validated but hard target, Degrade one CXXC reader, ChIP the fusion: the one experiment that settles whether the address is contested, Fractional occupancy needs a free concentration as well as a Kd, and nobody has measured either for a KMT2A fusion, Hypothesis: the cell-of-origin methylome, not the breakpoint, decides whether a KMT2A::AFF1 leukemia is HOXA-high or HOXA-low, Re-founding the address argument: the CXXC domain cannot specify a location at any affinity, and a tighter one would be worse, Step 1 — How the fusion finds its genes: AT-hooks and the CXXC domain reading unmethylated CpG, The 41 residues after the CXXC fold (1204-1244) carry a substantial part of the fusion's DNA grip, and removing them is why the structural literature's affinity is so low, The comparison that founded 'the CXXC contact is too weak' puts a 300 mM NaCl protein-DNA measurement against a 50 mM NaCl protein-peptide measurement, The CXXC domain (aa 1147-1195, PDB 2KKF) is a chromatin address, not a compartment address — CpG mutants lose transformation but keep their subnuclear position, The CXXC-DNA affinity is a ten-point ladder from 44 uM to 33 nM, not two numbers 1,300-fold apart, and every step but the last is under 5.5-fold, The MLL-protected Hoxa9 CpG sites bind the CXXC domain 4- to 9-fold tighter than the unprotected ones, in one ITC series at fixed everything else
499. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20159978
     Hsp90 directly modulates the spatial distribution of AF9/MLLT3 and affects target gene expression.

     Lin JJ, Hemenway CS · J Biol Chem 2010
     used by AF9's nuclear residence is chaperone-dependent, the Hsp90 site is the SAME C-terminal region the fusion keeps, and UniProt records no cytoplasmic pool at all, MLLT3 / AF9 — a famous fusion partner that is not a dependency, and a hub domain that is
500. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20395419
     Self-association mediated by the Ras association 1 domain of AF6 activates the oncogenic potential of MLL-AF6

     Liedtke M, Ayton PM, Somervaille TCP, Smith KS, Cleary ML · Blood 2010
     used by AFDN (AF6): nothing is discarded from the fusion, yet this is the clearest subtraction in the set — the fusion steals wild-type AF6 out of the cytoplasm, AFDN / AF6 — domain architecture and residue coordinates, Hypothesis — the elongation hijack is how one partner class satisfies a more general requirement, and the general requirement is what should be drugged, Import class 5: evidence borrowed from fusions that are not KMT2A fusions at all, KMT2A::AFDN (MLL-AF6), t(6;11)(q27;q23), Separation-of-function test: does KMT2A::AFF1 need its C-terminal homology domain to dimerise?, What is actually conserved across KMT2A partner classes — forced self-association, with two documented exceptions that break the rule
501. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20153263
     A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription

     Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary ML · Cancer Cell 2010
     used by AFDN (AF6): nothing is discarded from the fusion, yet this is the clearest subtraction in the set — the fusion steals wild-type AF6 out of the cytoplasm, AFF1 / AF4 — the 3' half of the fusion, and a target with almost no structural footing, AFF1 AF4_int motif to AF9/ENL AHD: the index fusion's only documented elongation interface, and it competes with DOT1L, AFF1 as the subtraction control: the refutation is WITHDRAWN - the degron is lost, not retained, AFF1 occupancy does not distinguish fusion-occupied promoters from wild-type KMT2A promoters in primary infant KMT2A::AFF1 - reproduced at promoter resolution, and the corpus should stop reading a partner ChIP as a fusion readout, AFF4 — the textbook SEC scaffold that KMT2A::AFF1 cells need LESS than other leukemias, Attribution audit 1 of 5 - who co-purifies with KMT2A::AFF1: the inventory does not survive, the individual partner blots mostly do, Attribution audit 5 of 5 - where KMT2A::AFF1 sits on chromatin: the field's standard attribution heuristic is invalidated by the paper that founded it, but two real survivors exist, CCNT1 / cyclin T1 — the regulatory half of P-TEFb, and the one part of the elongation core with any dependency variance, Does KMT2A::AFF1 deliver DOT1L to the AHD or displace it? A competition experiment in t(4;11) cells, DOT1L and H3K79 in KMT2A::MLLT1: a direct partner contact, mutually exclusive with the elongation complex, and the only fusion with a DOT1L-inhibitor complete remission, How much of this graph's mechanism is somebody else's fusion? A counted answer: 54% of fusion-bearing evidence, and 0% from a dedicated human KMT2A::AFF1 experiment, IntAct curates 47 interactions against engineered MLL fusion proteins, and every accession-keyed query in this project is blind to all of them - while its PSICQUIC mirror stops at 2024, KMT2A::MLLT1 engages P-TEFb through one 66-residue surface: the ENL AHD, residues 494-559, and L550E breaks it, KMT2A::MLLT1 versus KMT2A::MLLT3: paralogous partners whose chromosomes break on opposite sides of the same domain, Knock a tag-plus-degron cassette into the endogenous KMT2A::AFF1 allele in SEM - one construct that makes five claim classes attributable, MLLT3 / AF9 — a famous fusion partner that is not a dependency, and a hub domain that is, P-TEFb (CDK9 + cyclin T1) — the deepest dependency and the clearest therapeutic-index wall in the interactome, Partner import: when a mechanism measured in one fusion is asserted about another, Partner-protein occupancy is not fusion occupancy: every KMT2A::AFF1 chromatin claim resting on an AFF1, AFF4 or SEC-subunit ChIP is an upper bound that includes free complex, SEC — the AFF1/AFF4-scaffolded super elongation complex, the particle KMT2A::AFF1 is a permanent subunit of, Step 3 — The hijack: the fusion drags the super elongation complex to paused RNA polymerase II, The five verdicts in one place, plus what this beat read and did not use, The index fusion's 3' partner has ONE observed binary interaction in IntAct and forty-two residues of solved structure - every SEC contact attributed to AFF1 is an AFF4 result wearing AFF1's name, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The order in which the fusion's programme collapses is a property of the partner, not of KMT2A - so there is no single causal chain, This corpus argued from the literature that intersecting fusion peaks with partner peaks cannot attribute occupancy, and eighty cycles later a beat measured that partner antibody sitting at the negative control in primary patient samples - two independent derivations from the same paper, with no edge between them and one wrong premise, Where KMT2A::MLLT1 actually sits: chromatin occupancy is mapped, subnuclear localisation of the endogenous fusion has never been imaged
502. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20159561
     AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia

     Lin C, Smith ER, Takahashi H, et al. · Molecular Cell 2010
     used by AFF1 / AF4 — the 3' half of the fusion, and a target with almost no structural footing, AFF4 — the textbook SEC scaffold that KMT2A::AFF1 cells need LESS than other leukemias, AFF4 has never been placed in a haematopoietic cell state — every SEC cell-state result is in another tissue, CCNT1 / cyclin T1 — the regulatory half of P-TEFb, and the one part of the elongation core with any dependency variance, ELL — rank 7 on selectivity and the deepest common-essential in the top ten, with one NMR fragment to its name, ELL2 — a SEC subunit that almost no cell needs, next to a paralogue almost every cell needs, Experiment: does KMT2A::AFF1 form condensates at endogenous levels, and does it need them? The separation-of-function and IDR-swap test, Hypothesis — forced-oligomerisation interfaces are the mutation-resistant drug targets the fusion field has been ignoring, Hypothesis: KMT2A::AFF1 does not require phase separation — recruitment biochemistry is sufficient, and the condensate model does not transfer from NUP98/ENL, KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), Mechanism class 1 — chromatin and elongation hijack (KMT2A-r, NUP98-r), Mechanism class 4 — condensate-driven transcriptional rewiring (NUP98-r, EWSR1::FLI1), P-TEFb (CDK9 + cyclin T1) — the deepest dependency and the clearest therapeutic-index wall in the interactome, Plain-English: what transcription elongation is, and why a traffic light explains this leukemia, SEC — the AFF1/AFF4-scaffolded super elongation complex, the particle KMT2A::AFF1 is a permanent subunit of, Step 3 — The hijack: the fusion drags the super elongation complex to paused RNA polymerase II, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, Where KMT2A and its fusions sit inside the nucleus — SNL1/SNL2, nuclear speckles and the condensate question
503. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20575032
     A specific linkage between the incidence of TP53 mutations and type of chromosomal translocations in B-precursor acute lymphoblastic leukemia cell lines

     Inukai T, Zhang X, Kameyama T, et al. · American Journal of Hematology 2010
     used by ALL-PO (CVCL_1069) — an infant KMT2A::AFF1 line that is already in DepMap and has never been screened, The KOCL series (CVCL_3993, CVCL_6867, CVCL_3994, CVCL_3995) — four Japanese infant KMT2A::AFF1 lines, all under one year
504. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 20838408
     Tackling the widespread and critical impact of batch effects in high-throughput data

     Leek JT, Scharpf RB, Bravo HC, Simcha D, Langmead B, Johnson WE, Geman D, Baggerly K, Irizarry RA · Nature Reviews Genetics 11:733-739 2010
     used by An anchored comparison keeps the nuisance sample on both sides, which is how you ask whether a PAIR is special rather than whether a SAMPLE is unusual, GSE252378 carries an institution-level batch effect: unrelated pairs from the same hospital overlap more than cross-hospital pairs, and a cohort-median comparator absorbs that into the same-patient claim
505. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20159607
     MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele.

     Thiel AT, Blessington P, Zou T, et al. · Cancer Cell 2010
     used by An anti-MLL-N antibody sees the wild-type allele and the direct fusion, and nothing else - and cannot rank them, ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, Does the fusion 'lose restraint'? The pattern of KMT2A-side loss, and why the tidy reading does not survive contact with the ledger, DPY30 — the smallest COMPASS subunit, and the only one that behaves like a selective dependency, Experiment: induce CyP33 in a KMT2A-rearranged cell and ask, allele by allele, whether the brake still works at HOXA9, Experiment: titrate wild-type KMT2A up and down in one leukemia cell and watch what happens to the fusion's grip on chromatin, Hypothesis: the fusion is exempt from KMT2A's regulation, not free of it - the brakes still operate at the same loci, on the other allele, Hypothesis: what the KMT2A half loses is control of its own abundance, not control of its activity, Import class 1: murine MLL-AF9 myeloid transformation, the field's default assay and this graph's largest single import, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: the WIN motif and the whole WRAD interface (aa 3762-3767, Arg3765), RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum, Redesign: the proximity-labelling map of KMT2A::AFF1 cannot be controlled with the wild-type allele - it has to be controlled with time, Settle the WRAD question: tagged co-IP plus degron-timed proximity across three fusion classes, The lost SET domain, and the verdict: the fusion is a gain-of-function neomorph, not a KMT2A loss-of-function, The third category: modules lost from the fusion protein but supplied in trans by the wild-type KMT2A allele, WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away, What could refute the menin-interface bet, restated after the provenance audit: three tests, none of which is about menin binding, WRAD reaches KMT2A fusions only as a passenger on a recruited wild-type complex
506. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20961854
     Molecular basis of the mixed lineage leukemia-menin interaction: implications for targeting mixed lineage leukemias

     Grembecka J, Belcher AM, Hartley T, et al. · Journal of Biological Chemistry 2010
     used by Analysis (runnable): can a menin ligand tell KMT2A from JUND? A structural and co-folding selectivity profile of the whole inhibitor class, Hypothesis: menin inhibitors differ in how much JUND they liberate, and the least JUND-liberating compound will be the most durable, In a competitive menin-binding scaffold with assumed rates, the drug exposure needed scales with menin relative to the fusion-menin Kd, and whether recovery after a lapse lags collapse is governed by the drug's residence time - a conditional counter-lead to the pulsed-dosing premise, not a prediction, KMT2B (MLL2/MLL4) - the other protein menin binds, and the one this graph never wrote, MBM2, the second menin-binding motif of KMT2A (residues 23-40): 26-fold weaker than MBM1, never separately co-crystallised, and the only part of the menin grip a drug is not aimed at, Measure the menin-KMT2B affinity nobody has measured, and the four clinical inhibitors' IC50 against it, Menin holds KMT2A and KMT2B, and the graph has been written as if it held one, Severability (contract law) — what survives when a clause is struck, and what survives a KMT2A break, The comparison that founded 'the CXXC contact is too weak' puts a 300 mM NaCl protein-DNA measurement against a 50 mM NaCl protein-peptide measurement, The menin–KMT2A grip (MBM1), the interface the drugs actually block
507. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20541448
     Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis

     Milne TA, Kim J, Wang GG, Stadler SC, Basrur V, Whitcomb SJ, Wang Z, Ruthenburg AJ, Elenitoba-Johnson KSJ, Roeder RG, Allis CD · Molecular Cell 38:853-63 2010
     used by ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, CXXC-DNA interface of the KMT2A fusion: a validated but hard target, Does the fusion 'lose restraint'? The pattern of KMT2A-side loss, and why the tidy reading does not survive contact with the ledger, DPY30 — the smallest COMPASS subunit, and the only one that behaves like a selective dependency, Experiment: induce CyP33 in a KMT2A-rearranged cell and ask, allele by allele, whether the brake still works at HOXA9, Experiment: titrate wild-type KMT2A up and down in one leukemia cell and watch what happens to the fusion's grip on chromatin, Hypothesis: the fusion is exempt from KMT2A's regulation, not free of it - the brakes still operate at the same loci, on the other allele, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein, RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, Redesign: the proximity-labelling map of KMT2A::AFF1 cannot be controlled with the wild-type allele - it has to be controlled with time, The fusion junction itself as a small-molecule target: a candid verdict, The third category: modules lost from the fusion protein but supplied in trans by the wild-type KMT2A allele, WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away, WDR5: an established wild-type KMT2A contact, and no fusion contact ever measured, WRAD reaches KMT2A fusions only as a passenger on a recruited wild-type complex
508. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20211137
     Distinct factors control histone variant H3.3 localization at specific genomic regions.

     Goldberg AD, Banaszynski LA, Noh KM, et al. · Cell 2010
     used by Assay telomere maintenance across the thirteen B-lineage ALL DepMap lines, and see whether it predicts the DAXX dependency split, ATRX - DAXX's partner and the other arm of H3.3 deposition; in this disease its only signal is in the four lymphoid cell lines, H3.3 - the graph's most-named epigenetic object with no entry, 325 mentions, and not one measurement in a KMT2A-rearranged cell, HIRA - the chaperone that puts new H3.3 into transcribed gene bodies, and therefore the machine that runs this graph's clearance clock, Histone H3.3 - one protein, two genes, and the reason this graph should not file it as gene-h3f3a
509. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20818375
     Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint.

     Liu H, et al. · Nature 2010
     used by ATR phosphorylates KMT2A at S516 to break the SCF(Skp2) contact - a phospho-gated degradation switch sitting inside the retained fragment, Attribution audit 2 of 5 - post-translational modifications on KMT2A::AFF1: nothing survives at peptide level, and the one strong PTM result is explicitly about the wild-type protein, S821 is not phosphorylated in any dataset we could query: the 14-3-3 motif candidate is dead as stated, SCF(Skp2) grips the retained fragment and the fusion escapes it - the clearest documented non-menin contact on that region, SKP2 - the substrate receptor that grips the retained fragment; two nodes in this graph already pointed at it as a free-text string with nothing to point to, The non-synchronisable state: five KMT2A-rearranged lines refuse mimosine, double thymidine and nocodazole, and the fusion protein does not fluctuate through the cycle
510. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20156954
     Summarizing historical information on controls in clinical trials

     Neuenschwander B, Capkun-Niggli G, Branson M, Spiegelhalter DJ · Clinical Trials 2010
     used by Bayesian borrowing: how many infants a prior is worth, and when it lies, What 160 infants a year actually permits: the sample-size arithmetic
511. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 21091149
     Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new and emerging treatment options

     Schultz KR, Prestidge T, Camitta B · Expert Rev Hematol 2010
     used by BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11)
512. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21059956
     Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene.

     Yang Y, Gurung B, Wu T, Wang H, Stoffers DA, Hua X · Proceedings of the National Academy of Sciences USA 2010
     used by Both approved menin inhibitors cause multi-organ hyperplasia in animals, and one of them in the pancreas irreversibly, Four different ways to lose menin, and the graph has been treating them as one, How long does menin have to be gone? Two months in a mouse islet, a decade or more in a human carrier, Pancreatic neuroendocrine tumours in MEN1: the manifestation that kills, and the one the animal data points at, Switching menin off reverses diabetes that is already there - in three different diabetic mouse models, The same drug target, pursued for benefit: menin inhibition is a diabetes strategy in the literature
513. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20729832
     Purified human BRCA2 stimulates RAD51-mediated recombination.

     Jensen RB, et al. · Nature 2010
     used by BRCA2 (P51587, 3,418 aa) - the RAD51 loader that receives the resected end BRCA1 licensed, named in 10 entries and never written; DepMap mean -0.519, and its 12-record KMT2A intersection is entirely germline-panel and pan-cancer sequencing with no mechanism
514. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20201073
     T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes.

     Dow EC, Liu H, Rice AP · J Cell Physiol 2010
     used by CDK9 - the kinase the whole SEC story runs through, which this graph held only as half of a two-protein summary entry
515. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20075868
     Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size.

     Müller C, Bremer A, Schreiber S, Eichwald S, Calkhoven CF · EMBO J 2010
     used by CEBPA — ranks 25th on the KMT2A scan and sits at the median of random genes
516. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20181089
     Roles for common MLL/COMPASS subunits and the 19S proteasome in regulating CIITA pIV and MHC class II gene expression and promoter methylation.

     Koues OI, Mehta NT, Truax AD, Dudley RK, Brooks JK, Greer SF · Epigenetics Chromatin 2010
     used by CIITA - the class II transactivator, a gene menin sits on, and the only antigen-presentation gene in this disease with a knockout that proves the drug acts through it, HLA-DR - a two-chain MHC class II heterodimer, so no single gene symbol denotes the surface marker a flow report calls HLA-DR, HLA-DRA - the non-polymorphic alpha chain, and the only HLA-DR chain any source on this beat names explicitly
517. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 19648166
     Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia.

     Zhao X, Singh S, Pardoux C, Zhao J, Hsi ED, Abo A, et al. · Haematologica 2010
     used by CLEC12A (CD371, CLL-1, MICL) - the leukaemic-stem-cell antigen whose therapeutic rationale rests on an absence, and which menin inhibition appears to induce
518. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20231472
     Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways

     Sanz E, Munoz-A N, Monserrat J, Van-Den-Rym A, Escoll P, Ranz I, et al., de-la-Hera A · Proceedings of the National Academy of Sciences USA 2010
     used by Common lymphoid progenitor (CLP) — the CD10-positive lymphoid route that infant KMT2A leukaemia appears NOT to take
519. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20194896
     The AF4.MLL fusion protein is capable of inducing ALL in mice without requirement of MLL.AF4.

     Bursen A, Schwabe K, Rüster B, et al. · Blood 2010
     used by Competing model 1: the reciprocal product starts the leukaemia and then leaves, Competing model 4: t(4;11) cells are addicted to the direct fusion and completely indifferent to the reciprocal one, Forty-five percent of t(4;11) patients express a KMT2A fusion transcript that keeps the whole WRAD interface, In the only panel that tested both halves of four translocations, 3 of 4 reciprocal fusions transformed and only 1 of 4 direct ones did, Menin primacy was established on the der(11) product alone and has never been tested against the der(4) product, SIAH1 — the E3 ligase that degrades AFF1, and that the reciprocal AF4::KMT2A fusion escapes, The infant breakpoint mutilates the reciprocal protein's first PHD finger - so 'the reciprocal product' is at least two different proteins, The reciprocal fusion (AFF1::KMT2A and friends): a second oncoprotein that opens chromatin for the first
520. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20541477
     The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.

     Muntean AG, Tan J, Sitwala K, Huang Y, Bronstein J, Connelly JA, Basrur V, Elenitoba-Johnson KS, Hess JL · Cancer Cell 2010
     used by Corrections owed to other beats: nine entries whose stated provenance is now resolvable, and one unflagged import, CTR9 — a PAF1C subunit the field assumes is a fusion partner, with no paper that tested it, H2B ubiquitination is upstream of the fusion's defining mark and is still not a target, because the fusion uses a general mechanism rather than a special one, Import class 1: murine MLL-AF9 myeloid transformation, the field's default assay and this graph's largest single import, LEO1 — the weakest-evidenced entry in the PAF1 complex, and the gene whose Ensembl id this project already got wrong once, Menin is the best handle on KMT2A::AFF1 because of where the break falls, not because menin is biologically special, PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein, PAF1C couples transcription to H2B ubiquitination - but the RTF1 half of that coupling is yeast-specific and contested in human cells, and PAF1C is one of the few complexes that genuinely binds the retained KMT2A fragment, RTF1 — the PAF1C subunit the graph was missing, on a complex that does bind the retained KMT2A fragment, Separation-of-function RTF1 rescue in a KMT2A-fusion line: does the fusion need PAF1C for elongation, or for H2B ubiquitination?, SKIC8 (formerly WDR61) — the last PAF1C subunit, and a gene-symbol trap worth recording, The lost SET domain, and the verdict: the fusion is a gain-of-function neomorph, not a KMT2A loss-of-function, The PAF complex species is mouse - and its only deposited series is Hoxa9-ER, not an MLL fusion at all
521. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20203130
     Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom).

     Mohan M, Herz HM, Takahashi YH, Lin C, Lai KC, Zhang Y, Washburn MP, Florens L, Shilatifard A · Genes & Development 2010
     used by CTNNB1 (beta-catenin) — the Wnt link inside DotCom, and the one piece of KMT2A biology that is not chromatin, KMT2A::MLLT6 (MLL-AF17), t(11;17)(q23;q12-q21) — the bridge case: a leucine zipper on a DOT1L-complex subunit, MLLT6 (AF17) — the fourth KMT2A fusion partner inside DotCom, and the only one no cell needs, TRRAP — a 3,859-residue DotCom subunit that every cell needs and no KMT2A cell needs more
522. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20339075
     The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.

     Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA · Science 2010
     used by CTNNB1 (beta-catenin) — the Wnt link inside DotCom, and the one piece of KMT2A biology that is not chromatin
523. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 2KKF: Solution structure of MLL CXXC domain in complex with palindromic CPG DNA

     Cierpicki T, Risner LE, Grembecka J, et al. · RCSB Protein Data Bank 2010
     used by CXXC to unmethylated CpG DNA: nine mapped contact residues, and an affinity that spans 44 uM to 33 nM depending on the construct, the DNA and the salt, CXXC-DNA interface of the KMT2A fusion: a validated but hard target
524. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 19951360
     CXXC finger protein 1 restricts the Setd1A histone H3K4 methyltransferase complex to euchromatin

     Tate CM, Lee JH, Skalnik DG · FEBS Journal 277(1):210-23 2010
     used by CXXC1 (CFP1) - a CpG-reading COMPASS subunit that binds MLL1 and recruits it to HoxA7, and whose CXXC domain cannot substitute for KMT2A's in a fusion
525. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20215641
     Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting.

     Schafer E, Irizarry R, Negi S, et al. · Blood 2010
     used by Decitabine - degrades DNMT1, and in ALL cells it degrades KMT2A too: the hypomethylating agent with two mechanisms and a menin-inhibitor combination already in the clinic, Decitabine's target is a pan-essential gene, and KMT2A-rearranged lines depend on it LESS than other leukaemia lines - rank 16,949 of 17,728, Put mutant IDH2 into SEM and ask three questions at once: does the unmethylated-CpG pool shrink, does the fusion move, and does its competitor move, The KMT2A-r DNA methylation signature — focal hypermethylation, no global hypomethylation, and a hypomethylating agent that did not help
526. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20423332
     Contribution of DEAH-box protein DHX16 in human pre-mRNA splicing.

     Gencheva M, Kato M, Newo AN, Lin RJ · Biochem J 2010
     used by DHX16 / hPRP2 (O60231) - the spliceosomal catalytic-activation helicase, pan-MLL-fusion, and one of only two in the 42 whose index-fusion p-value exceeds 0.05
527. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20471949
     HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP.

     Sobhian B, Laguette N, Yatim A, Nakamura M, Levy Y, Kiernan R, Benkirane M · Mol Cell 2010
     used by Directed extraction of P-TEFb from the reservoir: HIV-1 Tat is the worked example, and the only cellular candidate rests on one unreplicated paper
528. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20018852
     Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex

     Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC · Journal of Biological Chemistry 285(7):4268-72 2010
     used by Does WDR5 move between complexes? An acute KANSL1 degron with WDR5 co-IP, WDR5 CUT&RUN and H4K5/K8/K16ac readout in a KMT2A-rearranged line, KANSL1 - the NSL scaffold, and the protein through which WDR5 binding to NSL and to MLL/COMPASS is mutually exclusive, KANSL2 - the second NSL subunit in the WDR5 structure, with one leukaemia record and a dependency profile that is the mirror image of a selective target, MSL1 - the MSL scaffold that carries MOF and MSL2 to HOXA9 and MEIS1, with zero records against KMT2A and a mapped, drawable domain architecture, NSL complex - the MOF assembly that five NUP98 fusions bind alongside MLL1, and that competes with MLL/COMPASS for WDR5, WDR5 is partitioned, not shared: NSL and SET1/MLL complexes compete for one pool, so perturbing NSL changes how much WDR5 reaches the wild-type KMT2A complex the fusion depends on
529. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 21123134
     Detection of fusion genes at the protein level in leukemia patients via the flow cytometric immunobead assay.

     · Best Pract Res Clin Haematol 2010
     used by Eleven abstract-level bounded absences re-tested with the instrument that overturned the HDAC6 one - ten survive, one is not checkable this way, none overturned, No KMT2A fusion junction peptide has ever been reported - the one measurement that would prove the protein exists has not been published
530. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20937905
     ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.

     Ohno Y, Suto S, Yamanaka M, Mizutani Y, Mitsutake S, Igarashi Y, Sassa T, Kihara A · Proc Natl Acad Sci U S A 2010
     used by ELOVL1 - the fatty-acid elongase that infant MLL-AF4 ALL retains from its fetal origin, and the lipid enzyme on the opposite side of the divide from ACSL4
531. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20126984
     Secreted form of EphA7 in lung cancer

     Tsuboi M, Mori H, Bunai T, Kageyama S, Suzuki M, Okudela K, Takamochi K, Ogawa H, Niwa H, Shinmura K, Sugimura H · Int J Oncol 36:635-40 2010
     used by EPHA7 - ephrin type-A receptor 7, a published direct promoter target of the ALL1/AF4 (KMT2A::AFF1) fusion protein
532. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20887958
     Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators

     Wilson NK, Foster SD, Wang X, Knezevic K, Schütte J, Kaimakis P, Chilarska PM, Kinston S, et al. · Cell Stem Cell 7:532-544 2010
     used by ERG - a heptad stem-cell transcription factor whose 15 mentions in this graph are mostly about OTHER diseases, and whose best-established role in B-ALL is loss of function, not cooperation, GATA2 - the least KMT2A-selective gene on this beat, ranking 17,591 of 17,728, and a factor whose leukaemia biology is about stemness and chemoresistance rather than about the fusion, LMO2 (rhombotin-2) - a bridging LIM-only protein, higher in pro-B and MLL-rearranged B-ALL, anti-selective in KMT2A-rearranged lines, and a physical partner of the KDM5A module that NUP98::KDM5A retains
533. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20308673
     Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial

     Le Deley MC, Delattre O, Schaefer KL, et al. · Journal of Clinical Oncology 2010
     used by EWSR1::FLI1 (EWS-FLI1), t(11;22)(q24;q12)
534. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20541251
     Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression

     Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, Patel DJ · Cell 141(7):1183-1194 2010
     used by Experiment: induce CyP33 in a KMT2A-rearranged cell and ask, allele by allele, whether the brake still works at HOXA9, Hypothesis: the fusion is exempt from KMT2A's regulation, not free of it - the brakes still operate at the same loci, on the other allele, Lost from the KMT2A half: PHD3 and the bromodomain are one cassette, not two modules (aa 1566-1765), PHD3 and the CyP33 RRM: Kd 7-15 uM, and a 2023 ternary structure that settles the 2010 disagreement - H3K4me3 and the RRM CAN be held at once, and the real switch is RNA, PHD3 reading H3K4me3: Kd 4.3 uM for the PHD3-bromo cassette, 30 uM for PHD3 alone, two co-crystals - and the whole module is thrown away by the breakpoint
535. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20601953
     Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.

     Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, et al. · Nat Genet 2010
     used by EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off, Giving a translocation-promoting epigenetic drug in a translocation-defined B-lineage leukaemia, to infants
536. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20303345
     Additive and global functions of HoxA cluster genes in mesoderm derivatives

     Di-Poi N, Koch U, Radtke F, Duboule D · Developmental Biology 2010
     used by Fault trees, minimal cut sets and common-cause failure — reliability engineering on a buffered oncogenic program, Hypothesis: the fusion output program fails at a threshold on total cut-set suppression, so three nodes at 40% beat one node at 90%
537. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21113167
     The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.

     Katada S, Sassone-Corsi P · Nat Struct Mol Biol 2010
     used by H3K4me3 oscillates around the clock and MLL1 is what lets it - a cell state of KMT2A biology this project has never once mentioned, KMT2A / MLL1 — the gene that breaks
538. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 20735237
     Decoding the histone H4 lysine 20 methylation mark

     Balakrishnan L, Milavetz B · Critical Reviews in Biochemistry and Molecular Biology 2010
     used by H4K20me1 - the transcription- and replication-linked H4 state, whose gene-body level tracks Pol II; it HAS been profiled genome-wide in human haematopoietic stem cells twice, and a query scoped to 'leukemia' cannot see either dataset, H4K20me2 - the abundant repair-linked H4 mark, the 53BP1 docking site, and the first H4K20 state in this graph; never once measured in a KMT2A-rearranged cell
539. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20622854
     PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression

     Liu W, Tanasa B, Tyurina OV, et al. · Nature 2010
     used by H4K20me1 - the transcription- and replication-linked H4 state, whose gene-body level tracks Pol II; it HAS been profiled genome-wide in human haematopoietic stem cells twice, and a query scoped to 'leukemia' cannot see either dataset
540. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21172665
     TDRD3 is an effector molecule for arginine-methylated histone marks.

     Yang Y, Lu Y, Espejo A, Wu J, et al. · Mol Cell 2010
     used by H4R3me2a - the activating arginine mark that a KMT2-family enzyme's OWN tandem PHD module reads, where the Kabuki-syndrome mutations sit, and which no KMT2A-fusion study has ever measured, TDRD3 (Q9H7E2) - the reader the new H4R3me2a entry could not name, and it brings TOP3B to the MYC promoter and keeps R loops off it
541. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21072194
     Dynamic distribution of histone H4 arginine 3 methylation marks in the developing murine cortex.

     Chittka A · PLoS One 2010
     used by H4R3me2a - the activating arginine mark that a KMT2-family enzyme's OWN tandem PHD module reads, where the Kabuki-syndrome mutations sit, and which no KMT2A-fusion study has ever measured, H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system
542. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20154729
     In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium

     Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C · Nature 2010
     used by Haemogenic endothelium — the vessel-wall cell that gives birth to blood, Is KMT2A::AFF1 leukemia epithelial or endothelial? No — it is haematopoietic. But the question is a good one
543. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 20940258
     CLP-1 associates with MyoD and HDAC to restore skeletal muscle cell regeneration.

     Galatioto J, Mascareno E, Siddiqui MA · J Cell Sci 2010
     used by HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less
544. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20699226
     Kinetics of re-establishing H3K79 methylation marks in global human chromatin.

     Sweet SMM, Li M, Thomas PM, et al. · Journal of Biological Chemistry 2010
     used by Histone H3.3 - one protein, two genes, and the reason this graph should not file it as gene-h3f3a, Nobody has convincingly found the H3K79 eraser - and that constraint sets the clock on every DOT1L inhibitor, With no eraser, how fast the histone itself is replaced decides how much H3K79 methylation there is - and that sets the clock a DOT1L drug has to beat
545. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20082846
     Loss of let-7 binding sites resulting from truncations of the 3' untranslated region of HMGA2 mRNA in uterine leiomyomas.

     Klemke M, Meyer A, et al. · Cancer Genetics and Cytogenetics 2010
     used by HMGA2 (P52926) - a direct KMT2A::AFF1 target through the let-7b axis, and a recurrent fusion partner whose own fusions work by escaping a microRNA rather than by making a chimeric protein
546. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 19748670
     Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes.

     Santos J, Cerveira N, Bizarro S, et al. · Leuk Res 2010
     used by How a cytoskeletal partner reaches chromatin at all — the KMT2A N-terminus drags it in, and the traffic runs both ways, SEPTIN2 (septin-2 / NEDD5) — KMT2A fusion partner in t(2;11)(q37;q23)
547. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20394798
     Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling

     Soe-Lin S, Apte SS, Mikhael MR, Kayembe LK, Nie G, Ponka P · Experimental Hematology 2010
     used by Hypothesis: the haem and iron dependency of KMT2A-rearranged lines is monocytic physiology, not fusion biology — and the panel cannot tell us either way, Monocyte — the graph's most-discussed undefined cell identity, and the confound sitting under its own DepMap haem signal, Settle the monocytic confound isogenically: degrade the fusion, read haem-gene dependency before lineage has time to move
548. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20506279
     The structure of the FYR domain of transforming growth factor beta regulator 1

     Garcia-Alai MM, Allen MD, Joerger AC, Bycroft M · Protein Science 19(7):1432-1438 2010
     used by Hypothesis: what the KMT2A half loses is control of its own abundance, not control of its activity, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: the FYRN-FYRC clamp (2018-2074 / 3666-3747) that holds wild-type KMT2A together
549. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21048951
     ATM modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot.

     Sun J, Oma Y, Harata M, Kono K, Shima H, Kinomura A, et al. · PLoS One 5(10):e13554 2010
     used by If RPA loading at the KMT2A breakpoint cluster region is the licensing step for the etoposide-induced translocation, then the nuclear RPA reserve is a modifier of therapy-related KMT2A-rearranged leukaemia risk - and an ATR inhibitor, which kills by exhausting RPA, would raise that risk rather than lower it, No fusion oncoprotein in any family has a published replication-protein-A measurement: 23 queries across five fusion families and four spelling variants each, every querytranslation read back, zero records - so the PI's analogy dimension for RPA has no comparator at all, and the index fusion's single locus-level result is the entire field, RAD51 - the one repair protein measured AT the KMT2A translocation hotspot, and ATM controls how much of it loads there, Repeat the one published RPA-at-the-KMT2A-breakpoint experiment in a haematopoietic cell, with an RPA-dose arm - the protocol is fully specified in a 2010 paper whose every arm used fibroblasts and a CML line, and whose primer sets, dose and controls are all published, RPA1 and RPA2 are curated HGNC aliases of POLR1A and POLR1B, and RPA34 - a UniProt synonym of RPA2 - is an alias of POLR1G, so three of the ssDNA clamp's names point at RNA polymerase I subunits; the hazard is in symbol-based DATABASE lookups, not in PubMed, and the measured contamination says which, The replication protein A heterotrimer (RPA1/RPA2/RPA3) - the ssDNA clamp that every resection and replication-stress claim in this corpus silently depends on, and which had no entry until cycle 160, The rule-64 complex-form query that the RPA2 decline flagged as unrun has now been run, and it finds a published damage-state RPA occupancy measurement AT the KMT2A breakpoint cluster region - so two of this corpus's absence entries carry ids that are broader than the claims inside them
550. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20940255
     Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation.

     Pickard A, Wong PP, McCance DJ · J Cell Sci 2010
     used by KAT2B / PCAF - named in an existing entry's own id and never written, and the only acetyltransferase in this graph whose substrate is a fusion partner protein
551. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20417597
     CpG islands recruit a histone H3 lysine 36 demethylase.

     Blackledge NP, Zhou JC, et al. · Mol Cell 2010
     used by KDM2A - the CXXC reader that antagonises KMT2A leukaemogenesis, and displaces wild-type MLL rather than the fusion
552. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20633769
     A translocation in acute lymphoblastic leukemia that cytogenetically mimics the recurrent MLL-AFF1 translocation and fuses SEPT11 to MLL.

     Stevens SJ, Meers LE, Albrechts JC, et al. · Cancer Genet Cytogenet 2010
     used by KMT2A::SEPTIN11 (MLL-SEPT11) — the fusion that cytogenetically impersonates t(4;11)
553. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21156246
     Therapy-related acute myeloid leukemia with t(2;11)(q37;q23) after treatment for osteosarcoma.

     Bielorai B, Meyer C, Trakhtenbrot L, et al. · Cancer Genet Cytogenet 2010
     used by KMT2A::SEPTIN2 (MLL-SEPT2), t(2;11)(q37;q23) — the therapy-related septin
554. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 19838211
     MdmX is a substrate for the deubiquitinating enzyme USP2a.

     Allende-Vega N, Sparks A, Lane DP, Saville MK · Oncogene 2010
     used by KMT2A::USP2, inv(11)(q23.3q23.3) - the minor-BCR fusion that keeps the PHD fingers
555. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20711175
     Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

     Ng SB, Bigham AW, Buckingham KJ, et al. · Nat Genet 2010
     used by KMT2D (MLL2/MLL4) - the gene named in this graph's menin-resistance entry, written here for the first time, MLL2 and MLL4 each name two different genes, and the ambiguity is in the papers, not in the databases
556. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20543838
     Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development

     Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE · Nature Immunology 2010
     used by Lymphoid-primed multipotent progenitor (LMPP) — the bi-potent cell that explains how one fusion makes two lineages, Multipotent progenitor (MPP) — the stage where the undifferentiated KMT2A-r infant leukaemias map
557. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 19965632
     Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia.

     Stam RW, Den Boer ML, Schneider P, ..., Pieters R · Blood 2010
     used by MCL1 - named in 34 entries of this graph with no entry of its own until now; a mitochondrial survival protein high in infant KMT2A-rearranged ALL, druggable, and so far undruggable in patients, Prednisolone - the active steroid, the drug every resistance experiment in this disease actually used, and the one given into the spinal fluid, Prednisone - the prophase drug, the prognostic factor, and a prodrug that has never itself been tested on a KMT2A-rearranged blast
558. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20647761
     MCL-1 localizes to sites of DNA damage and regulates DNA damage response.

     Jamil S, et al. · Cell Cycle 2010;9:2843-55 2010
     used by MCL1 - named in 34 entries of this graph with no entry of its own until now; a mitochondrial survival protein high in infant KMT2A-rearranged ALL, druggable, and so far undruggable in patients
559. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20044539
     PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice

     Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B · Science 2010
     used by Meiotic recombination: hundreds of deliberate DNA breaks per cell, made by a topoisomerase relative, at sites chosen by a single zinc-finger protein
560. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20044541
     Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination

     Myers S, Bowden R, Tumian A, Bontrop RE, Freeman C, MacFie TS, McVean G, Donnelly P · Science 2010
     used by Meiotic recombination: hundreds of deliberate DNA breaks per cell, made by a topoisomerase relative, at sites chosen by a single zinc-finger protein
561. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20818382
     PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans

     Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L, May CA, Jeffreys AJ · Nature Genetics 2010
     used by Meiotic recombination: hundreds of deliberate DNA breaks per cell, made by a topoisomerase relative, at sites chosen by a single zinc-finger protein
562. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20677832
     The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL-mediated activation and repression.

     Park S, Osmers U, Raman G, Schwantes RH, Diaz MO, Bushweller JH · Biochemistry 2010
     used by Menin is the best handle on KMT2A::AFF1 because of where the break falls, not because menin is biologically special, PHD3 and the CyP33 RRM: Kd 7-15 uM, and a 2023 ternary structure that settles the 2010 disagreement - H3K4me3 and the RRM CAN be held at once, and the real switch is RNA, PHD3 reading H3K4me3: Kd 4.3 uM for the PHD3-bromo cassette, 30 uM for PHD3 alone, two co-crystals - and the whole module is thrown away by the breakpoint, PPIE (CyP33) — the off-switch the fusion throws away, and the reason PHD3 reinsertion kills transformation, What is lost: the PHD3/CYP33 switch that lets wild-type KMT2A turn itself off
563. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20969866
     Menin stimulates homology-directed DNA repair.

     Gallo A, Agnese S, Esposito I, Galgani M, Avvedimento VE · FEBS Letters 2010
     used by Menin stimulates homology-directed repair through Chk1 and the region required is 1-228: a 2010 paper that is cited in no entry of this graph and in no reference list of the 2026 paper that reports the same conclusion
564. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 19956200
     Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

     Forrest ARR, Kanamori-Katayama M, Tomaru Y, Lassmann T, Ninomiya N, Takahashi Y, de Hoon MJL, Kubosaki A, Kaiho A, Suzuki M, Yasuda J, Kawai J, Hayashizaki Y, Hume DA, Suzuki H · Leukemia 24(2):460-6 2010
     used by miR-9 — the most MLL-specific microRNA in AML, encoded at three separate loci nobody has disambiguated
565. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 21131038
     Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial.

     Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, et al. · Lancet 2010
     used by Mitoxantrone - the Interfant-06 protocol says it is less cardiotoxic than daunorubicin, and the largest survivor cohort ever assembled says it is about seventeen times worse per milligram
566. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21170927
     Widely expressed Af17 is likely not required for embryogenesis, hematopoiesis, and animal survival.

     Zhang Z, Huang L, Reisenauer MR, Wu H, Chen L, Zhang Y, Xia Y, Zhang W · Genesis 2010
     used by MLLT6 (AF17) — the fourth KMT2A fusion partner inside DotCom, and the only one no cell needs
567. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20051780
     Dense methylation of types 1 and 2 regulatory regions of the CD10 gene promoter in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene.

     Ikawa Y, ..., Saikawa Y · J Pediatr Hematol Oncol 2010
     used by MME / CD10 (CALLA) - the marker this disease is defined by NOT having, and the promoter is methylated shut rather than simply not yet switched on
568. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20628149
     Nomenclature of monocytes and dendritic cells in blood

     Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, et al., Lutz MB · Blood 2010
     used by Monocyte — the graph's most-discussed undefined cell identity, and the confound sitting under its own DepMap haem signal
569. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20305087
     A lentiviral functional proteomics approach identifies chromatin remodeling complexes important for the induction of pluripotency

     Mak AB, Ni Z, Hewel JA, Chen GI, Zhong G, Karamboulas K, Blakely K, Smiley S, Marcon E, Roudeva D, Li J, Olsen JB, Wan C, Punna T, Isserlin R, Chetyrkin S, Gingras AC, Emili A, Greenblatt J, Moffat J · Molecular & Cellular Proteomics 9(5):811-23 2010
     used by NELF — the brake that has to come off for elongation, absent from the KMT2A literature, and less required in KMT2A-rearranged lines than in any other leukaemia
570. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20703299
     Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

     Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. · Nature 2010
     used by Nestin+ mesenchymal stem cell — the niche cell that MLL-AF9 leukaemia wakes up and then loses, Sympathetic nerve fibre in bone marrow — the wiring that sets the niche's daily rhythm, through beta-3 in health and beta-2 in leukaemia, The bone-marrow niche — the address a blood stem cell lives at, which 26 entries in this graph invoke and none had defined
571. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20558618
     NUP98-MLL fusion in human acute myeloblastic leukemia

     Kaltenbach S, et al. · Blood 116(13):2332-2335 2010
     used by NUP98::KMT2A, inv(11)(p15q23) — the NUP98 fusion that contains KMT2A and is menin-inhibitor RESISTANT, Two classes of KMT2A rearrangement keep the SET domain, and the graph says otherwise
572. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB entry 3OOI: Crystal Structure of Human Histone-Lysine N-methyltransferase NSD1 SET domain in Complex with S-adenosyl-L-methionine (primary citation: The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation)

     RCSB Protein Data Bank · RCSB PDB 2010
     used by NUP98::NSD1, t(5;11)(q35;p15.5)
573. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20676058
     Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains

     Reynoird N, Schwartz BE, Delvecchio M, et al. · EMBO Journal 2010
     used by NUTM1 (NUT) - a testis-restricted, fully disordered protein that writes no mark and instead switches ON a writer, and the 3' partner of the KMT2A-wild-type infant B-ALL with the opposite prognosis
574. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
     GSE13159 - Microarray Innovations in Leukemia (MILE) study, stage 1 (per-sample GSM metadata)

     GEO depositors, series GSE13159 · NCBI Gene Expression Omnibus 2010
     used by Only one public B-lineage cohort annotates the KMT2A fusion PARTNER per sample beside an expression matrix - every other large paediatric leukaemia resource records only 'MLL yes/no' or the 11q23 band
575. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

     City of Hope Medical Center; National Cancer Institute · ClinicalTrials.gov 2010
     used by Panobinostat - the HDAC inhibitor this graph has reasoned about for cycles without having an entry for, with strong KMT2A-rearranged xenograft activity and a terminated adult trial, Panobinostat lowers H2B ubiquitination in MLL-rearranged ALL by suppressing RNF20/RNF40/WAC — the only clinical-stage agent that reaches this axis, and its one ALL trial was stopped for lack of efficacy
576. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 2KU7: Solution structure of MLL1 PHD3-Cyp33 RRM chimeric protein

     Wang Z, Song J, Milne TA, et al. · RCSB Protein Data Bank 2010
     used by PHD3 and the CyP33 RRM: Kd 7-15 uM, and a 2023 ternary structure that settles the 2010 disagreement - H3K4me3 and the RRM CAN be held at once, and the real switch is RNA
577. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 3LQJ: Crystal structure of MLL1 PHD3-Bromo complexed with H3(1-9)K4me3 peptide

     Wang Z, Song J, Milne TA, et al. · RCSB Protein Data Bank 2010
     used by PHD3 reading H3K4me3: Kd 4.3 uM for the PHD3-bromo cassette, 30 uM for PHD3 alone, two co-crystals - and the whole module is thrown away by the breakpoint
578. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20583997
     PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha.

     Bultsma Y, Keune WJ, Divecha N (3 authors; senior author Divecha N) · Biochem J 2010
     used by PIP4K2A - the lipid kinase at a genome-wide childhood-ALL susceptibility locus, whose product is the ligand a PHD finger reads
579. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20378816
     Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML

     Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de The H, Chen SJ, Chen Z · Science 2010
     used by PML::RARA, t(15;17)(q24;q21)
580. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20460131
     Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain.

     Hom RA, Chang PY, Roy S, Musselman CA, Glass KC, Selezneva AI, Gozani O, Ismagilov RF, Cleary ML, Kutateladze TG · Journal of Molecular Biology 2010
     used by PPIE (CyP33) — the off-switch the fusion throws away, and the reason PHD3 reinsertion kills transformation
581. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 19965660
     Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}.

     Qiu JJ, Lu X, Zeisig BB, Ma Z, Cai X, Chen S, Gronemeyer H, Tweardy DJ, So CW, Dong S · Blood 2010
     used by PRKAR1A (P10644) - a PKA regulatory subunit in the pan-MLL-fusion core with no catalytic subunit anywhere in the network, and a fusion oncogene in variant APL
582. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20869947
     Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration.

     Simarro M, Gimenez-Cassina A, Kedersha N, Lazaro JB, Adelmant GO, Marto JA, Rhee K, Tisdale S, Danial N, Benarafa C, Orduña A, Anderson P · Biochem Biophys Res Commun 2010
     used by PSIP1-FASTKD2 declined: the bait is a mitochondrial matrix and nucleoid protein with two experimental localisations, the prey is nucleoplasmic LEDGF, and the row is one spoke-expanded BioID2 proximity in K562
583. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20967262
     Expression of conjoined genes: another mechanism for gene regulation in eukaryotes

     Prakash T, Sharma VK, Adati N, Taylor TD, et al. · PLoS ONE 2010
     used by Read-through (cis-SAGe) chimeras: most 'fusions' called from RNA-seq in childhood ALL are normal conjoined genes
584. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20225261
     The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo

     Vandyke K, Dewar AL, Diamond P, Fitter S, Schultz CG, Sims NA, Zannettino ACW · Journal of Bone and Mineral Research 25(8):1759-70 2010
     used by Reading the same-source counter-evidence: 77 notes adjudicated, and the defect is not the one the metric measures
585. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20065082
     Combined interphase fluorescence in situ hybridization elucidates the genetic heterogeneity of T-cell acute lymphoblastic leukemia in adults.

     Gorello P, et al. · Haematologica 2010
     used by SET::NUP214 (TAF-Ibeta-NUP214, SET-CAN), cryptic del(9)(q34.11q34.13) - a HOXA-driving fusion of a histone chaperone to a nucleoporin, with no KMT2A and no menin-binding motif, SET::NUP214 is the second KMT2A-free HOXA fusion, and it converges on the same two proteins CALM-AF10 uses: CRM1 and DOT1L - and so does NPM1c, which IS menin-dependent (corrected 2026-09-21)
586. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 20701601
     Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfurt-Munster study group

     Harrison CJ, Haas O, Harbott J, Biondi A, Stanulla M, Trka J, Izraeli S · British Journal of Haematology 2010
     used by Step 3: the G-banded karyotype and t(4;11)(q21;q23), Step 4: the split-signal FISH nucleus - one fusion, one green, one red, Step 5: molecular confirmation and naming the partner
587. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20382164
     SUMOylation of the lens epithelium-derived growth factor/p75 attenuates its transcriptional activity on the heat shock protein 27 promoter.

     Bueno MT, et al. · J Mol Biol 2010
     used by SUMO1 - not a complex partner of LEDGF but a modifier of it, and the interactome row cannot tell you which
588. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 19906718
     The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression.

     Yang YJ, Han JW, Youn HD, Cho EJ · Nucleic Acids Research 2010
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
589. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 19881540
     Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition.

     Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR · Oncogene 2010
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
590. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 21318185
     Deletion of the Men1 gene prevents streptozotocin-induced hyperglycemia in mice.

     Yang Y, Wang H, Hua X · Experimental Diabetes Research 2010
     used by Switching menin off reverses diabetes that is already there - in three different diabetic mouse models
591. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 21103407
     The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/β-catenin coactivators essential for intestinal homeostasis.

     Mahmoudi T, et al. · PLoS Biol 2010
     used by TCF7L2 - the protein IntAct's 'DOT1L-TCF4' row is actually about, and the Wnt effector that DOT1L and AF10 coactivate, The DOT1L partner IntAct calls TCF4 is TCF7L2 - the second UTP18/WDR5-class symbol mis-assignment found in this interactome, and gene-tcf4 is declined
592. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20686504
     Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT

     · Leukemia 2010
     used by TERT — telomerase, switched on by the index fusion through HOXA7
593. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20484083
     c-Myb, Menin, GATA-3, and MLL form a dynamic transcription complex that plays a pivotal role in human T helper type 2 cell development.

     Nakata Y, Brignier AC, Jin S, Shen Y, Rudnick SI, Sugita M, Gewirtz AM · Blood 2010
     used by Th17 cell - the mature CD4 T-helper subset whose differentiation and maintenance require MENIN, which makes it the clearest published on-target normal-tissue liability of the menin interface
594. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20574452
     Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells

     Daniels TR, Neacato II, Rodriguez JA, Pandha HS, Morgan R, Penichet ML · Leukemia 24:1555-1565 2010
     used by The HOX-PBX interface, and its one peptide: HXR9/HTL001 has been tried in eight tumour types and in KMT2A-rearranged leukaemia exactly once
595. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 20400950
     Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1

     Vezzoli A, Bonadies N, Allen MD, et al. · Nature Structural and Molecular Biology 2010
     used by The LEDGF PWWP–H3K36me nucleosome contact: how the fusion learns its address
596. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20513434
     Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation

     Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, Graf S, Flicek P, Kerkhoven RM, van Lohuizen M, Reinders M, Wessels L, van Steensel B · Molecular Cell 2010
     used by The nuclear lamina and lamina-associated domains - evidence grade for KMT2A: weak and indirect, not none
597. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     Expression data from murine cell line transduced with epitope tagged forms of Hoxa9 (GSE21299)

     GEO submitters · NCBI Gene Expression Omnibus 2010
     used by The PAF complex species is mouse - and its only deposited series is Hoxa9-ER, not an MLL fusion at all
598. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 20442396
     A modified "cross-talk" between histone H2B Lys-120 ubiquitination and H3 Lys-79 methylation.

     Darwanto A, Curtis MP, Schrag M, Kirsch W, Liu P, Xu G, Neidigh JW, Zhang K · J Biol Chem 2010
     used by The trans-histone crosstalk H2Bub → DOT1L → H3K79me: modulatory for me1, effectively required for me2/me3
599. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20219906
     Novel type II transmembrane serine proteases, MSPL and TMPRSS13, Proteolytically activate membrane fusion activity of the hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.

     Okumura Y, Takahashi E, Yano M et al · Journal of Virology 2010
     used by TMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
600. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 20407419
     Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.

     Krull S, Dorries J, Boysen B, Reidenbach S, Magnius L, et al. · EMBO J 2010
     used by TPR / Megator (P12270) - the nuclear-basket nucleoporin that builds heterochromatin exclusion zones, in the pan-MLL-fusion core